Skip to main content
Top
Published in: Journal of Hematology & Oncology 1/2023

Open Access 01-12-2023 | Targeted Therapy | Review

Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics

Authors: Hao-Ran Jin, Jin Wang, Zi-Jing Wang, Ming-Jia Xi, Bi-Han Xia, Kai Deng, Jin-Lin Yang

Published in: Journal of Hematology & Oncology | Issue 1/2023

Login to get access

Abstract

Lipid metabolic reprogramming is an emerging hallmark of cancer. In order to sustain uncontrolled proliferation and survive in unfavorable environments that lack oxygen and nutrients, tumor cells undergo metabolic transformations to exploit various ways of acquiring lipid and increasing lipid oxidation. In addition, stromal cells and immune cells in the tumor microenvironment also undergo lipid metabolic reprogramming, which further affects tumor functional phenotypes and immune responses. Given that lipid metabolism plays a critical role in supporting cancer progression and remodeling the tumor microenvironment, targeting the lipid metabolism pathway could provide a novel approach to cancer treatment. This review seeks to: (1) clarify the overall landscape and mechanisms of lipid metabolic reprogramming in cancer, (2) summarize the lipid metabolic landscapes within stromal cells and immune cells in the tumor microenvironment, and clarify their roles in tumor progression, and (3) summarize potential therapeutic targets for lipid metabolism, and highlight the potential for combining such approaches with other anti-tumor therapies to provide new therapeutic opportunities for cancer patients.
Literature
1.
go back to reference Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.PubMed Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.PubMed
2.
go back to reference Rohrig F, Schulze A. The multifaceted roles of fatty acid synthesis in cancer. Nat Rev Cancer. 2016;16(11):732–49.PubMed Rohrig F, Schulze A. The multifaceted roles of fatty acid synthesis in cancer. Nat Rev Cancer. 2016;16(11):732–49.PubMed
3.
go back to reference Shang S, Liu J, Hua F. Protein acylation: mechanisms, biological functions and therapeutic targets. Signal Transduct Target Ther. 2022;7(1):396.PubMedPubMedCentral Shang S, Liu J, Hua F. Protein acylation: mechanisms, biological functions and therapeutic targets. Signal Transduct Target Ther. 2022;7(1):396.PubMedPubMedCentral
4.
go back to reference Koundouros N, Poulogiannis G. Reprogramming of fatty acid metabolism in cancer. Br J Cancer. 2020;122(1):4–22.PubMed Koundouros N, Poulogiannis G. Reprogramming of fatty acid metabolism in cancer. Br J Cancer. 2020;122(1):4–22.PubMed
5.
go back to reference Strickaert A, Saiselet M, Dom G, De Deken X, Dumont JE, Feron O, Sonveaux P, Maenhaut C. Cancer heterogeneity is not compatible with one unique cancer cell metabolic map. Oncogene. 2017;36(19):2637–42.PubMed Strickaert A, Saiselet M, Dom G, De Deken X, Dumont JE, Feron O, Sonveaux P, Maenhaut C. Cancer heterogeneity is not compatible with one unique cancer cell metabolic map. Oncogene. 2017;36(19):2637–42.PubMed
6.
go back to reference Liu Y, Cao X. Characteristics and significance of the pre-metastatic niche. Cancer Cell. 2016;30(5):668–81.PubMed Liu Y, Cao X. Characteristics and significance of the pre-metastatic niche. Cancer Cell. 2016;30(5):668–81.PubMed
7.
go back to reference Bader JE, Voss K, Rathmell JC. Targeting metabolism to improve the tumor microenvironment for cancer immunotherapy. Mol Cell. 2020;78(6):1019–33.PubMedPubMedCentral Bader JE, Voss K, Rathmell JC. Targeting metabolism to improve the tumor microenvironment for cancer immunotherapy. Mol Cell. 2020;78(6):1019–33.PubMedPubMedCentral
8.
go back to reference Wang H, Franco F, Tsui YC, Xie X, Trefny MP, Zappasodi R, Mohmood SR, Fernandez-Garcia J, Tsai CH, Schulze I, et al. CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors. Nat Immunol. 2020;21(3):298–308.PubMedPubMedCentral Wang H, Franco F, Tsui YC, Xie X, Trefny MP, Zappasodi R, Mohmood SR, Fernandez-Garcia J, Tsai CH, Schulze I, et al. CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors. Nat Immunol. 2020;21(3):298–308.PubMedPubMedCentral
9.
go back to reference Wu L, Zhang X, Zheng L, Zhao H, Yan G, Zhang Q, Zhou Y, Lei J, Zhang J, Wang J, et al. RIPK3 orchestrates fatty acid metabolism in tumor-associated macrophages and hepatocarcinogenesis. Cancer Immunol Res. 2020;8(5):710–21.PubMed Wu L, Zhang X, Zheng L, Zhao H, Yan G, Zhang Q, Zhou Y, Lei J, Zhang J, Wang J, et al. RIPK3 orchestrates fatty acid metabolism in tumor-associated macrophages and hepatocarcinogenesis. Cancer Immunol Res. 2020;8(5):710–21.PubMed
10.
go back to reference Veglia F, Tyurin VA, Blasi M, De Leo A, Kossenkov AV, Donthireddy L, To TKJ, Schug Z, Basu S, Wang F, et al. Fatty acid transport protein 2 reprograms neutrophils in cancer. Nature. 2019;569(7754):73–8.PubMedPubMedCentral Veglia F, Tyurin VA, Blasi M, De Leo A, Kossenkov AV, Donthireddy L, To TKJ, Schug Z, Basu S, Wang F, et al. Fatty acid transport protein 2 reprograms neutrophils in cancer. Nature. 2019;569(7754):73–8.PubMedPubMedCentral
11.
go back to reference Xu S, Chaudhary O, Rodriguez-Morales P, Sun X, Chen D, Zappasodi R, Xu Z, Pinto AFM, Williams A, Schulze I, et al. Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8(+) T cells in tumors. Immunity. 2021;54(7):1561-1577 e1567.PubMedPubMedCentral Xu S, Chaudhary O, Rodriguez-Morales P, Sun X, Chen D, Zappasodi R, Xu Z, Pinto AFM, Williams A, Schulze I, et al. Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8(+) T cells in tumors. Immunity. 2021;54(7):1561-1577 e1567.PubMedPubMedCentral
12.
go back to reference Niavarani SR, Lawson C, Bakos O, Boudaud M, Batenchuk C, Rouleau S, Tai LH. Lipid accumulation impairs natural killer cell cytotoxicity and tumor control in the postoperative period. BMC Cancer. 2019;19(1):823.PubMedPubMedCentral Niavarani SR, Lawson C, Bakos O, Boudaud M, Batenchuk C, Rouleau S, Tai LH. Lipid accumulation impairs natural killer cell cytotoxicity and tumor control in the postoperative period. BMC Cancer. 2019;19(1):823.PubMedPubMedCentral
13.
go back to reference Schcolnik-Cabrera A, Chavez-Blanco A, Dominguez-Gomez G, Taja-Chayeb L, Morales-Barcenas R, Trejo-Becerril C, Perez-Cardenas E, Gonzalez-Fierro A, Duenas-Gonzalez A. Orlistat as a FASN inhibitor and multitargeted agent for cancer therapy. Expert Opin Investig Drugs. 2018;27(5):475–89.PubMed Schcolnik-Cabrera A, Chavez-Blanco A, Dominguez-Gomez G, Taja-Chayeb L, Morales-Barcenas R, Trejo-Becerril C, Perez-Cardenas E, Gonzalez-Fierro A, Duenas-Gonzalez A. Orlistat as a FASN inhibitor and multitargeted agent for cancer therapy. Expert Opin Investig Drugs. 2018;27(5):475–89.PubMed
14.
go back to reference Wang Y, Lu JH, Wang F, Wang YN, He MM, Wu QN, Lu YX, Yu HE, Chen ZH, Zhao Q, et al. Inhibition of fatty acid catabolism augments the efficacy of oxaliplatin-based chemotherapy in gastrointestinal cancers. Cancer Lett. 2020;473:74–89.PubMed Wang Y, Lu JH, Wang F, Wang YN, He MM, Wu QN, Lu YX, Yu HE, Chen ZH, Zhao Q, et al. Inhibition of fatty acid catabolism augments the efficacy of oxaliplatin-based chemotherapy in gastrointestinal cancers. Cancer Lett. 2020;473:74–89.PubMed
15.
go back to reference Ruan C, Meng Y, Song H. CD36: an emerging therapeutic target for cancer and its molecular mechanisms. J Cancer Res Clin Oncol. 2022;148(7):1551–8.PubMed Ruan C, Meng Y, Song H. CD36: an emerging therapeutic target for cancer and its molecular mechanisms. J Cancer Res Clin Oncol. 2022;148(7):1551–8.PubMed
16.
go back to reference Zhang C, Liao Y, Liu P, Du Q, Liang Y, Ooi S, Qin S, He S, Yao S, Wang W. FABP5 promotes lymph node metastasis in cervical cancer by reprogramming fatty acid metabolism. Theranostics. 2020;10(15):6561–80.PubMedPubMedCentral Zhang C, Liao Y, Liu P, Du Q, Liang Y, Ooi S, Qin S, He S, Yao S, Wang W. FABP5 promotes lymph node metastasis in cervical cancer by reprogramming fatty acid metabolism. Theranostics. 2020;10(15):6561–80.PubMedPubMedCentral
17.
go back to reference Bensaad K, Favaro E, Lewis CA, Peck B, Lord S, Collins JM, Pinnick KE, Wigfield S, Buffa FM, Li JL, et al. Fatty acid uptake and lipid storage induced by HIF-1alpha contribute to cell growth and survival after hypoxia-reoxygenation. Cell Rep. 2014;9(1):349–65.PubMed Bensaad K, Favaro E, Lewis CA, Peck B, Lord S, Collins JM, Pinnick KE, Wigfield S, Buffa FM, Li JL, et al. Fatty acid uptake and lipid storage induced by HIF-1alpha contribute to cell growth and survival after hypoxia-reoxygenation. Cell Rep. 2014;9(1):349–65.PubMed
18.
go back to reference Zhang M, Di Martino JS, Bowman RL, Campbell NR, Baksh SC, Simon-Vermot T, Kim IS, Haldeman P, Mondal C, Yong-Gonzales V, et al. Adipocyte-derived lipids mediate melanoma progression via FATP proteins. Cancer Discov. 2018;8(8):1006–25.PubMedPubMedCentral Zhang M, Di Martino JS, Bowman RL, Campbell NR, Baksh SC, Simon-Vermot T, Kim IS, Haldeman P, Mondal C, Yong-Gonzales V, et al. Adipocyte-derived lipids mediate melanoma progression via FATP proteins. Cancer Discov. 2018;8(8):1006–25.PubMedPubMedCentral
19.
go back to reference Mendes C, Lopes-Coelho F, Ramos C, Martins F, Santos I, Rodrigues A, Silva F, Andre S, Serpa J. Unraveling FATP1, regulated by ER-beta, as a targeted breast cancer innovative therapy. Sci Rep. 2019;9(1):14107.PubMedPubMedCentral Mendes C, Lopes-Coelho F, Ramos C, Martins F, Santos I, Rodrigues A, Silva F, Andre S, Serpa J. Unraveling FATP1, regulated by ER-beta, as a targeted breast cancer innovative therapy. Sci Rep. 2019;9(1):14107.PubMedPubMedCentral
20.
go back to reference Wang D, Ye Q, Gu H, Chen Z. The role of lipid metabolism in tumor immune microenvironment and potential therapeutic strategies. Front Oncol. 2022;12: 984560.PubMedPubMedCentral Wang D, Ye Q, Gu H, Chen Z. The role of lipid metabolism in tumor immune microenvironment and potential therapeutic strategies. Front Oncol. 2022;12: 984560.PubMedPubMedCentral
21.
go back to reference Snaebjornsson MT, Janaki-Raman S, Schulze A. Greasing the wheels of the cancer machine: the role of lipid metabolism in cancer. Cell Metab. 2020;31(1):62–76.PubMed Snaebjornsson MT, Janaki-Raman S, Schulze A. Greasing the wheels of the cancer machine: the role of lipid metabolism in cancer. Cell Metab. 2020;31(1):62–76.PubMed
22.
go back to reference Khwairakpam AD, Banik K, Girisa S, Shabnam B, Shakibaei M, Fan L, Arfuso F, Monisha J, Wang H, Mao X, et al. The vital role of ATP citrate lyase in chronic diseases. J Mol Med (Berl). 2020;98(1):71–95.PubMed Khwairakpam AD, Banik K, Girisa S, Shabnam B, Shakibaei M, Fan L, Arfuso F, Monisha J, Wang H, Mao X, et al. The vital role of ATP citrate lyase in chronic diseases. J Mol Med (Berl). 2020;98(1):71–95.PubMed
23.
go back to reference Comerford SA, Huang Z, Du X, Wang Y, Cai L, Witkiewicz AK, Walters H, Tantawy MN, Fu A, Manning HC, et al. Acetate dependence of tumors. Cell. 2014;159(7):1591–602.PubMedPubMedCentral Comerford SA, Huang Z, Du X, Wang Y, Cai L, Witkiewicz AK, Walters H, Tantawy MN, Fu A, Manning HC, et al. Acetate dependence of tumors. Cell. 2014;159(7):1591–602.PubMedPubMedCentral
24.
go back to reference Jones SF, Infante JR. Molecular pathways: fatty acid synthase. Clin Cancer Res. 2015;21(24):5434–8.PubMed Jones SF, Infante JR. Molecular pathways: fatty acid synthase. Clin Cancer Res. 2015;21(24):5434–8.PubMed
25.
go back to reference Ferraro GB, Ali A, Luengo A, Kodack DP, Deik A, Abbott KL, Bezwada D, Blanc L, Prideaux B, Jin X, et al. Fatty acid synthesis is required for breast cancer brain metastasis. Nat Cancer. 2021;2(4):414–28.PubMedPubMedCentral Ferraro GB, Ali A, Luengo A, Kodack DP, Deik A, Abbott KL, Bezwada D, Blanc L, Prideaux B, Jin X, et al. Fatty acid synthesis is required for breast cancer brain metastasis. Nat Cancer. 2021;2(4):414–28.PubMedPubMedCentral
26.
go back to reference Zhao J, Zhi Z, Wang C, Xing H, Song G, Yu X, Zhu Y, Wang X, Zhang X, Di Y. Exogenous lipids promote the growth of breast cancer cells via CD36. Oncol Rep. 2017;38(4):2105–15.PubMedPubMedCentral Zhao J, Zhi Z, Wang C, Xing H, Song G, Yu X, Zhu Y, Wang X, Zhang X, Di Y. Exogenous lipids promote the growth of breast cancer cells via CD36. Oncol Rep. 2017;38(4):2105–15.PubMedPubMedCentral
27.
go back to reference Ascenzi F, De Vitis C, Maugeri-Sacca M, Napoli C, Ciliberto G, Mancini R. SCD1, autophagy and cancer: implications for therapy. J Exp Clin Cancer Res. 2021;40(1):265.PubMedPubMedCentral Ascenzi F, De Vitis C, Maugeri-Sacca M, Napoli C, Ciliberto G, Mancini R. SCD1, autophagy and cancer: implications for therapy. J Exp Clin Cancer Res. 2021;40(1):265.PubMedPubMedCentral
28.
go back to reference Cluntun AA, Lukey MJ, Cerione RA, Locasale JW. Glutamine metabolism in cancer: understanding the heterogeneity. Trends Cancer. 2017;3(3):169–80.PubMedPubMedCentral Cluntun AA, Lukey MJ, Cerione RA, Locasale JW. Glutamine metabolism in cancer: understanding the heterogeneity. Trends Cancer. 2017;3(3):169–80.PubMedPubMedCentral
29.
go back to reference Jin J, Byun JK, Choi YK, Park KG. Targeting glutamine metabolism as a therapeutic strategy for cancer. Exp Mol Med. 2023;55(4):706–15.PubMedPubMedCentral Jin J, Byun JK, Choi YK, Park KG. Targeting glutamine metabolism as a therapeutic strategy for cancer. Exp Mol Med. 2023;55(4):706–15.PubMedPubMedCentral
30.
go back to reference Hui S, Ghergurovich JM, Morscher RJ, Jang C, Teng X, Lu W, Esparza LA, Reya T, Le Z, Yanxiang Guo J, et al. Glucose feeds the TCA cycle via circulating lactate. Nature. 2017;551(7678):115–8.PubMedPubMedCentral Hui S, Ghergurovich JM, Morscher RJ, Jang C, Teng X, Lu W, Esparza LA, Reya T, Le Z, Yanxiang Guo J, et al. Glucose feeds the TCA cycle via circulating lactate. Nature. 2017;551(7678):115–8.PubMedPubMedCentral
31.
go back to reference Ippolito L, Comito G, Parri M, Iozzo M, Duatti A, Virgilio F, Lorito N, Bacci M, Pardella E, Sandrini G, et al. Lactate rewires lipid metabolism and sustains a metabolic-epigenetic axis in prostate cancer. Cancer Res. 2022;82(7):1267–82.PubMedPubMedCentral Ippolito L, Comito G, Parri M, Iozzo M, Duatti A, Virgilio F, Lorito N, Bacci M, Pardella E, Sandrini G, et al. Lactate rewires lipid metabolism and sustains a metabolic-epigenetic axis in prostate cancer. Cancer Res. 2022;82(7):1267–82.PubMedPubMedCentral
32.
go back to reference Perez-Escuredo J, Dadhich RK, Dhup S, Cacace A, Van Hee VF, De Saedeleer CJ, Sboarina M, Rodriguez F, Fontenille MJ, Brisson L, et al. Lactate promotes glutamine uptake and metabolism in oxidative cancer cells. Cell Cycle. 2016;15(1):72–83.PubMed Perez-Escuredo J, Dadhich RK, Dhup S, Cacace A, Van Hee VF, De Saedeleer CJ, Sboarina M, Rodriguez F, Fontenille MJ, Brisson L, et al. Lactate promotes glutamine uptake and metabolism in oxidative cancer cells. Cell Cycle. 2016;15(1):72–83.PubMed
33.
go back to reference Broadfield LA, Pane AA, Talebi A, Swinnen JV, Fendt SM. Lipid metabolism in cancer: new perspectives and emerging mechanisms. Dev Cell. 2021;56(10):1363–93.PubMed Broadfield LA, Pane AA, Talebi A, Swinnen JV, Fendt SM. Lipid metabolism in cancer: new perspectives and emerging mechanisms. Dev Cell. 2021;56(10):1363–93.PubMed
34.
go back to reference Butler LM, Perone Y, Dehairs J, Lupien LE, de Laat V, Talebi A, Loda M, Kinlaw WB, Swinnen JV. Lipids and cancer: emerging roles in pathogenesis, diagnosis and therapeutic intervention. Adv Drug Deliv Rev. 2020;159:245–93.PubMedPubMedCentral Butler LM, Perone Y, Dehairs J, Lupien LE, de Laat V, Talebi A, Loda M, Kinlaw WB, Swinnen JV. Lipids and cancer: emerging roles in pathogenesis, diagnosis and therapeutic intervention. Adv Drug Deliv Rev. 2020;159:245–93.PubMedPubMedCentral
36.
go back to reference Gallagher EJ, Zelenko Z, Neel BA, Antoniou IM, Rajan L, Kase N, LeRoith D. Elevated tumor LDLR expression accelerates LDL cholesterol-mediated breast cancer growth in mouse models of hyperlipidemia. Oncogene. 2017;36(46):6462–71.PubMedPubMedCentral Gallagher EJ, Zelenko Z, Neel BA, Antoniou IM, Rajan L, Kase N, LeRoith D. Elevated tumor LDLR expression accelerates LDL cholesterol-mediated breast cancer growth in mouse models of hyperlipidemia. Oncogene. 2017;36(46):6462–71.PubMedPubMedCentral
37.
go back to reference Kim HY, Bae SJ, Choi JW, Han S, Bae SH, Cheong JH, Jang H. Cholesterol synthesis is important for breast cancer cell tumor sphere formation and invasion. Biomedicines. 2022;10(8):1908.PubMedPubMedCentral Kim HY, Bae SJ, Choi JW, Han S, Bae SH, Cheong JH, Jang H. Cholesterol synthesis is important for breast cancer cell tumor sphere formation and invasion. Biomedicines. 2022;10(8):1908.PubMedPubMedCentral
38.
39.
go back to reference Kopecka J, Trouillas P, Gasparovic AC, Gazzano E, Assaraf YG, Riganti C. Phospholipids and cholesterol: inducers of cancer multidrug resistance and therapeutic targets. Drug Resist Updat. 2020;49: 100670.PubMed Kopecka J, Trouillas P, Gasparovic AC, Gazzano E, Assaraf YG, Riganti C. Phospholipids and cholesterol: inducers of cancer multidrug resistance and therapeutic targets. Drug Resist Updat. 2020;49: 100670.PubMed
40.
go back to reference Glunde K, Bhujwalla ZM, Ronen SM. Choline metabolism in malignant transformation. Nat Rev Cancer. 2011;11(12):835–48.PubMedPubMedCentral Glunde K, Bhujwalla ZM, Ronen SM. Choline metabolism in malignant transformation. Nat Rev Cancer. 2011;11(12):835–48.PubMedPubMedCentral
41.
go back to reference Saito RF, Andrade LNS, Bustos SO, Chammas R. Phosphatidylcholine-derived lipid mediators: the crosstalk between cancer cells and immune cells. Front Immunol. 2022;13: 768606.PubMedPubMedCentral Saito RF, Andrade LNS, Bustos SO, Chammas R. Phosphatidylcholine-derived lipid mediators: the crosstalk between cancer cells and immune cells. Front Immunol. 2022;13: 768606.PubMedPubMedCentral
42.
go back to reference Iorio E, Ricci A, Bagnoli M, Pisanu ME, Castellano G, Di Vito M, Venturini E, Glunde K, Bhujwalla ZM, Mezzanzanica D, et al. Activation of phosphatidylcholine cycle enzymes in human epithelial ovarian cancer cells. Cancer Res. 2010;70(5):2126–35.PubMedPubMedCentral Iorio E, Ricci A, Bagnoli M, Pisanu ME, Castellano G, Di Vito M, Venturini E, Glunde K, Bhujwalla ZM, Mezzanzanica D, et al. Activation of phosphatidylcholine cycle enzymes in human epithelial ovarian cancer cells. Cancer Res. 2010;70(5):2126–35.PubMedPubMedCentral
43.
go back to reference Hernando E, Sarmentero-Estrada J, Koppie T, Belda-Iniesta C, Ramirez de Molina V, Cejas P, Ozu C, Le C, Sanchez JJ, Gonzalez-Baron M, et al. A critical role for choline kinase-alpha in the aggressiveness of bladder carcinomas. Oncogene. 2009;28(26):2425–35.PubMedPubMedCentral Hernando E, Sarmentero-Estrada J, Koppie T, Belda-Iniesta C, Ramirez de Molina V, Cejas P, Ozu C, Le C, Sanchez JJ, Gonzalez-Baron M, et al. A critical role for choline kinase-alpha in the aggressiveness of bladder carcinomas. Oncogene. 2009;28(26):2425–35.PubMedPubMedCentral
44.
go back to reference Sulciner ML, Gartung A, Gilligan MM, Serhan CN, Panigrahy D. Targeting lipid mediators in cancer biology. Cancer Metastasis Rev. 2018;37(2–3):557–72.PubMed Sulciner ML, Gartung A, Gilligan MM, Serhan CN, Panigrahy D. Targeting lipid mediators in cancer biology. Cancer Metastasis Rev. 2018;37(2–3):557–72.PubMed
45.
go back to reference Shindou H, Hishikawa D, Harayama T, Yuki K, Shimizu T. Recent progress on acyl CoA: lysophospholipid acyltransferase research. J Lipid Res. 2009;50(Suppl):S46-51.PubMedPubMedCentral Shindou H, Hishikawa D, Harayama T, Yuki K, Shimizu T. Recent progress on acyl CoA: lysophospholipid acyltransferase research. J Lipid Res. 2009;50(Suppl):S46-51.PubMedPubMedCentral
46.
go back to reference Hisano Y, Hla T. Bioactive lysolipids in cancer and angiogenesis. Pharmacol Ther. 2019;193:91–8.PubMed Hisano Y, Hla T. Bioactive lysolipids in cancer and angiogenesis. Pharmacol Ther. 2019;193:91–8.PubMed
47.
48.
go back to reference Petan T. Lipid droplets in cancer. Rev Physiol Biochem Pharmacol. 2023;185:53–86.PubMed Petan T. Lipid droplets in cancer. Rev Physiol Biochem Pharmacol. 2023;185:53–86.PubMed
49.
go back to reference Moldavski O, Amen T, Levin-Zaidman S, Eisenstein M, Rogachev I, Brandis A, Kaganovich D, Schuldiner M. Lipid droplets are essential for efficient clearance of cytosolic inclusion bodies. Dev Cell. 2015;33(5):603–10.PubMed Moldavski O, Amen T, Levin-Zaidman S, Eisenstein M, Rogachev I, Brandis A, Kaganovich D, Schuldiner M. Lipid droplets are essential for efficient clearance of cytosolic inclusion bodies. Dev Cell. 2015;33(5):603–10.PubMed
50.
go back to reference Cheng X, Geng F, Pan M, Wu X, Zhong Y, Wang C, Tian Z, Cheng C, Zhang R, Puduvalli V, et al. Targeting DGAT1 ameliorates glioblastoma by increasing fat catabolism and oxidative stress. Cell Metab. 2020;32(2):229-242 e228.PubMedPubMedCentral Cheng X, Geng F, Pan M, Wu X, Zhong Y, Wang C, Tian Z, Cheng C, Zhang R, Puduvalli V, et al. Targeting DGAT1 ameliorates glioblastoma by increasing fat catabolism and oxidative stress. Cell Metab. 2020;32(2):229-242 e228.PubMedPubMedCentral
51.
go back to reference Wilcock DJ, Badrock AP, Wong CW, Owen R, Guerin M, Southam AD, Johnston H, Telfer BA, Fullwood P, Watson J, et al. Oxidative stress from DGAT1 oncoprotein inhibition in melanoma suppresses tumor growth when ROS defenses are also breached. Cell Rep. 2022;39(12): 110995.PubMedPubMedCentral Wilcock DJ, Badrock AP, Wong CW, Owen R, Guerin M, Southam AD, Johnston H, Telfer BA, Fullwood P, Watson J, et al. Oxidative stress from DGAT1 oncoprotein inhibition in melanoma suppresses tumor growth when ROS defenses are also breached. Cell Rep. 2022;39(12): 110995.PubMedPubMedCentral
52.
go back to reference Zhang R, Meng J, Yang S, Liu W, Shi L, Zeng J, Chang J, Liang B, Liu N, Xing D. Recent advances on the role of ATGL in cancer. Front Oncol. 2022;12: 944025.PubMedPubMedCentral Zhang R, Meng J, Yang S, Liu W, Shi L, Zeng J, Chang J, Liang B, Liu N, Xing D. Recent advances on the role of ATGL in cancer. Front Oncol. 2022;12: 944025.PubMedPubMedCentral
53.
go back to reference Rossi T, Zamponi R, Chirico M, Pisanu ME, Iorio E, Torricelli F, Gugnoni M, Ciarrocchi A, Pistoni M. BETi enhance ATGL expression and its lipase activity to exert their antitumoral effects in triple-negative breast cancer (TNBC) cells. J Exp Clin Cancer Res. 2023;42(1):7.PubMedPubMedCentral Rossi T, Zamponi R, Chirico M, Pisanu ME, Iorio E, Torricelli F, Gugnoni M, Ciarrocchi A, Pistoni M. BETi enhance ATGL expression and its lipase activity to exert their antitumoral effects in triple-negative breast cancer (TNBC) cells. J Exp Clin Cancer Res. 2023;42(1):7.PubMedPubMedCentral
55.
go back to reference Povero D, Johnson SM, Liu J. Hypoxia, hypoxia-inducible gene 2 (HIG2)/HILPDA, and intracellular lipolysis in cancer. Cancer Lett. 2020;493:71–9.PubMed Povero D, Johnson SM, Liu J. Hypoxia, hypoxia-inducible gene 2 (HIG2)/HILPDA, and intracellular lipolysis in cancer. Cancer Lett. 2020;493:71–9.PubMed
56.
go back to reference Yin H, Li W, Mo L, Deng S, Lin W, Ma C, Luo Z, Luo C, Hong H. Adipose triglyceride lipase promotes the proliferation of colorectal cancer cells via enhancing the lipolytic pathway. J Cell Mol Med. 2021;25(8):3963–75.PubMedPubMedCentral Yin H, Li W, Mo L, Deng S, Lin W, Ma C, Luo Z, Luo C, Hong H. Adipose triglyceride lipase promotes the proliferation of colorectal cancer cells via enhancing the lipolytic pathway. J Cell Mol Med. 2021;25(8):3963–75.PubMedPubMedCentral
57.
go back to reference Wang YY, Attane C, Milhas D, Dirat B, Dauvillier S, Guerard A, Gilhodes J, Lazar I, Alet N, Laurent V, et al. Mammary adipocytes stimulate breast cancer invasion through metabolic remodeling of tumor cells. JCI Insight. 2017;2(4): e87489.PubMedPubMedCentral Wang YY, Attane C, Milhas D, Dirat B, Dauvillier S, Guerard A, Gilhodes J, Lazar I, Alet N, Laurent V, et al. Mammary adipocytes stimulate breast cancer invasion through metabolic remodeling of tumor cells. JCI Insight. 2017;2(4): e87489.PubMedPubMedCentral
58.
go back to reference Iftikhar R, Penrose HM, King AN, Samudre JS, Collins ME, Hartono AB, Lee SB, Lau F, Baddoo M, Flemington EF, et al. Elevated ATGL in colon cancer cells and cancer stem cells promotes metabolic and tumorigenic reprogramming reinforced by obesity. Oncogenesis. 2021;10(11):82.PubMedPubMedCentral Iftikhar R, Penrose HM, King AN, Samudre JS, Collins ME, Hartono AB, Lee SB, Lau F, Baddoo M, Flemington EF, et al. Elevated ATGL in colon cancer cells and cancer stem cells promotes metabolic and tumorigenic reprogramming reinforced by obesity. Oncogenesis. 2021;10(11):82.PubMedPubMedCentral
59.
go back to reference Padanad MS, Konstantinidou G, Venkateswaran N, Melegari M, Rindhe S, Mitsche M, Yang C, Batten K, Huffman KE, Liu J, et al. Fatty acid oxidation mediated by Acyl-CoA synthetase long chain 3 is required for mutant kras lung tumorigenesis. Cell Rep. 2016;16(6):1614–28.PubMedPubMedCentral Padanad MS, Konstantinidou G, Venkateswaran N, Melegari M, Rindhe S, Mitsche M, Yang C, Batten K, Huffman KE, Liu J, et al. Fatty acid oxidation mediated by Acyl-CoA synthetase long chain 3 is required for mutant kras lung tumorigenesis. Cell Rep. 2016;16(6):1614–28.PubMedPubMedCentral
60.
go back to reference Wang L, Li C, Song Y, Yan Z. Inhibition of carnitine palmitoyl transferase 1A-induced fatty acid oxidation suppresses cell progression in gastric cancer. Arch Biochem Biophys. 2020;696: 108664.PubMed Wang L, Li C, Song Y, Yan Z. Inhibition of carnitine palmitoyl transferase 1A-induced fatty acid oxidation suppresses cell progression in gastric cancer. Arch Biochem Biophys. 2020;696: 108664.PubMed
61.
go back to reference Nimmakayala RK, Leon F, Rachagani S, Rauth S, Nallasamy P, Marimuthu S, Shailendra GK, Chhonker YS, Chugh S, Chirravuri R, et al. Metabolic programming of distinct cancer stem cells promotes metastasis of pancreatic ductal adenocarcinoma. Oncogene. 2021;40(1):215–31.PubMed Nimmakayala RK, Leon F, Rachagani S, Rauth S, Nallasamy P, Marimuthu S, Shailendra GK, Chhonker YS, Chugh S, Chirravuri R, et al. Metabolic programming of distinct cancer stem cells promotes metastasis of pancreatic ductal adenocarcinoma. Oncogene. 2021;40(1):215–31.PubMed
62.
go back to reference Stockwell BR, Jiang X, Gu W. Emerging mechanisms and disease relevance of ferroptosis. Trends Cell Biol. 2020;30(6):478–90.PubMedPubMedCentral Stockwell BR, Jiang X, Gu W. Emerging mechanisms and disease relevance of ferroptosis. Trends Cell Biol. 2020;30(6):478–90.PubMedPubMedCentral
63.
go back to reference Dierge E, Debock E, Guilbaud C, Corbet C, Mignolet E, Mignard L, Bastien E, Dessy C, Larondelle Y, Feron O. Peroxidation of n-3 and n-6 polyunsaturated fatty acids in the acidic tumor environment leads to ferroptosis-mediated anticancer effects. Cell Metab. 2021;33(8):1701-1715 e1705.PubMed Dierge E, Debock E, Guilbaud C, Corbet C, Mignolet E, Mignard L, Bastien E, Dessy C, Larondelle Y, Feron O. Peroxidation of n-3 and n-6 polyunsaturated fatty acids in the acidic tumor environment leads to ferroptosis-mediated anticancer effects. Cell Metab. 2021;33(8):1701-1715 e1705.PubMed
64.
go back to reference Danielli M, Perne L, Jarc Jovicic E, Petan T. Lipid droplets and polyunsaturated fatty acid trafficking: balancing life and death. Front Cell Dev Biol. 2023;11:1104725.PubMedPubMedCentral Danielli M, Perne L, Jarc Jovicic E, Petan T. Lipid droplets and polyunsaturated fatty acid trafficking: balancing life and death. Front Cell Dev Biol. 2023;11:1104725.PubMedPubMedCentral
65.
go back to reference Martin-Perez M, Urdiroz-Urricelqui U, Bigas C, Benitah SA. The role of lipids in cancer progression and metastasis. Cell Metab. 2022;34(11):1675–99.PubMed Martin-Perez M, Urdiroz-Urricelqui U, Bigas C, Benitah SA. The role of lipids in cancer progression and metastasis. Cell Metab. 2022;34(11):1675–99.PubMed
66.
go back to reference Liao P, Wang W, Wang W, Kryczek I, Li X, Bian Y, Sell A, Wei S, Grove S, Johnson JK, et al. CD8(+) T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4. Cancer Cell. 2022;40(4):365-378 e366.PubMedPubMedCentral Liao P, Wang W, Wang W, Kryczek I, Li X, Bian Y, Sell A, Wei S, Grove S, Johnson JK, et al. CD8(+) T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4. Cancer Cell. 2022;40(4):365-378 e366.PubMedPubMedCentral
67.
go back to reference Wang C, Shi M, Ji J, Cai Q, Zhao Q, Jiang J, Liu J, Zhang H, Zhu Z, Zhang J. Stearoyl-CoA desaturase 1 (SCD1) facilitates the growth and anti-ferroptosis of gastric cancer cells and predicts poor prognosis of gastric cancer. Aging (Albany NY). 2020;12(15):15374–91.PubMed Wang C, Shi M, Ji J, Cai Q, Zhao Q, Jiang J, Liu J, Zhang H, Zhu Z, Zhang J. Stearoyl-CoA desaturase 1 (SCD1) facilitates the growth and anti-ferroptosis of gastric cancer cells and predicts poor prognosis of gastric cancer. Aging (Albany NY). 2020;12(15):15374–91.PubMed
68.
go back to reference Luo H, Wang X, Song S, Wang Y, Dan Q, Ge H. Targeting stearoyl-coa desaturase enhances radiation induced ferroptosis and immunogenic cell death in esophageal squamous cell carcinoma. Oncoimmunology. 2022;11(1):2101769.PubMedPubMedCentral Luo H, Wang X, Song S, Wang Y, Dan Q, Ge H. Targeting stearoyl-coa desaturase enhances radiation induced ferroptosis and immunogenic cell death in esophageal squamous cell carcinoma. Oncoimmunology. 2022;11(1):2101769.PubMedPubMedCentral
69.
go back to reference Yi J, Zhu J, Wu J, Thompson CB, Jiang X. Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis. Proc Natl Acad Sci. 2020;117(49):31189–97.PubMedPubMedCentral Yi J, Zhu J, Wu J, Thompson CB, Jiang X. Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis. Proc Natl Acad Sci. 2020;117(49):31189–97.PubMedPubMedCentral
70.
go back to reference Dong F, Mo Z, Eid W, Courtney KC, Zha X. Akt inhibition promotes ABCA1-mediated cholesterol efflux to ApoA-I through suppressing mTORC1. PLoS ONE. 2014;9(11): e113789.PubMedPubMedCentral Dong F, Mo Z, Eid W, Courtney KC, Zha X. Akt inhibition promotes ABCA1-mediated cholesterol efflux to ApoA-I through suppressing mTORC1. PLoS ONE. 2014;9(11): e113789.PubMedPubMedCentral
71.
go back to reference Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT. The PI3K pathway in human disease. Cell. 2017;170(4):605–35.PubMedPubMedCentral Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT. The PI3K pathway in human disease. Cell. 2017;170(4):605–35.PubMedPubMedCentral
72.
go back to reference Calvisi DF, Wang C, Ho C, Ladu S, Lee SA, Mattu S, Destefanis G, Delogu S, Zimmermann A, Ericsson J, et al. Increased lipogenesis, induced by AKT-mTORC1-RPS6 signaling, promotes development of human hepatocellular carcinoma. Gastroenterology. 2011;140(3):1071–83.PubMed Calvisi DF, Wang C, Ho C, Ladu S, Lee SA, Mattu S, Destefanis G, Delogu S, Zimmermann A, Ericsson J, et al. Increased lipogenesis, induced by AKT-mTORC1-RPS6 signaling, promotes development of human hepatocellular carcinoma. Gastroenterology. 2011;140(3):1071–83.PubMed
73.
go back to reference Li L, Pilo GM, Li X, Cigliano A, Latte G, Che L, Joseph C, Mela M, Wang C, Jiang L, et al. Inactivation of fatty acid synthase impairs hepatocarcinogenesis driven by AKT in mice and humans. J Hepatol. 2016;64(2):333–41.PubMed Li L, Pilo GM, Li X, Cigliano A, Latte G, Che L, Joseph C, Mela M, Wang C, Jiang L, et al. Inactivation of fatty acid synthase impairs hepatocarcinogenesis driven by AKT in mice and humans. J Hepatol. 2016;64(2):333–41.PubMed
74.
go back to reference Janku F, Yap TA, Meric-Bernstam F. Targeting the PI3K pathway in cancer: are we making headway? Nat Rev Clin Oncol. 2018;15(5):273–91.PubMed Janku F, Yap TA, Meric-Bernstam F. Targeting the PI3K pathway in cancer: are we making headway? Nat Rev Clin Oncol. 2018;15(5):273–91.PubMed
75.
go back to reference Yue S, Li J, Lee SY, Lee HJ, Shao T, Song B, Cheng L, Masterson TA, Liu X, Ratliff TL, et al. Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. Cell Metab. 2014;19(3):393–406.PubMedPubMedCentral Yue S, Li J, Lee SY, Lee HJ, Shao T, Song B, Cheng L, Masterson TA, Liu X, Ratliff TL, et al. Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. Cell Metab. 2014;19(3):393–406.PubMedPubMedCentral
76.
go back to reference Chen H, Qi Q, Wu N, Wang Y, Feng Q, Jin R, Jiang L. Aspirin promotes RSL3-induced ferroptosis by suppressing mTOR/SREBP-1/SCD1-mediated lipogenesis in PIK3CA-mutatnt colorectal cancer. Redox Biol. 2022;55: 102426.PubMedPubMedCentral Chen H, Qi Q, Wu N, Wang Y, Feng Q, Jin R, Jiang L. Aspirin promotes RSL3-induced ferroptosis by suppressing mTOR/SREBP-1/SCD1-mediated lipogenesis in PIK3CA-mutatnt colorectal cancer. Redox Biol. 2022;55: 102426.PubMedPubMedCentral
77.
go back to reference Chen LL, Wang WJ. p53 regulates lipid metabolism in cancer. Int J Biol Macromol. 2021;192:45–54.PubMed Chen LL, Wang WJ. p53 regulates lipid metabolism in cancer. Int J Biol Macromol. 2021;192:45–54.PubMed
78.
go back to reference Liu J, Zhang C, Hu W, Feng Z. Tumor suppressor p53 and metabolism. J Mol Cell Biol. 2019;11(4):284–92.PubMed Liu J, Zhang C, Hu W, Feng Z. Tumor suppressor p53 and metabolism. J Mol Cell Biol. 2019;11(4):284–92.PubMed
79.
go back to reference Jiang P, Du W, Wang X, Mancuso A, Gao X, Wu M, Yang X. p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase. Nat Cell Biol. 2011;13(3):310–6.PubMedPubMedCentral Jiang P, Du W, Wang X, Mancuso A, Gao X, Wu M, Yang X. p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase. Nat Cell Biol. 2011;13(3):310–6.PubMedPubMedCentral
80.
go back to reference Moon SH, Huang CH, Houlihan SL, Regunath K, Freed-Pastor WA, Morris JPT, Tschaharganeh DF, Kastenhuber ER, Barsotti AM, Culp-Hill R, et al. p53 represses the mevalonate pathway to mediate tumor suppression. Cell. 2019;176(3):564-580 e519.PubMed Moon SH, Huang CH, Houlihan SL, Regunath K, Freed-Pastor WA, Morris JPT, Tschaharganeh DF, Kastenhuber ER, Barsotti AM, Culp-Hill R, et al. p53 represses the mevalonate pathway to mediate tumor suppression. Cell. 2019;176(3):564-580 e519.PubMed
81.
go back to reference Sanchez-Macedo N, Feng J, Faubert B, Chang N, Elia A, Rushing EJ, Tsuchihara K, Bungard D, Berger SL, Jones RG, et al. Depletion of the novel p53-target gene carnitine palmitoyltransferase 1C delays tumor growth in the neurofibromatosis type I tumor model. Cell Death Differ. 2013;20(4):659–68.PubMedPubMedCentral Sanchez-Macedo N, Feng J, Faubert B, Chang N, Elia A, Rushing EJ, Tsuchihara K, Bungard D, Berger SL, Jones RG, et al. Depletion of the novel p53-target gene carnitine palmitoyltransferase 1C delays tumor growth in the neurofibromatosis type I tumor model. Cell Death Differ. 2013;20(4):659–68.PubMedPubMedCentral
82.
go back to reference Wahlstrom T, Henriksson MA. Impact of MYC in regulation of tumor cell metabolism. Biochim Biophys Acta. 2015;1849(5):563–9.PubMed Wahlstrom T, Henriksson MA. Impact of MYC in regulation of tumor cell metabolism. Biochim Biophys Acta. 2015;1849(5):563–9.PubMed
83.
go back to reference Gouw AM, Margulis K, Liu NS, Raman SJ, Mancuso A, Toal GG, Tong L, Mosley A, Hsieh AL, Sullivan DK, et al. The MYC oncogene cooperates with sterol-regulated element-binding protein to regulate lipogenesis essential for neoplastic growth. Cell Metab. 2019;30(3):556-572 e555.PubMedPubMedCentral Gouw AM, Margulis K, Liu NS, Raman SJ, Mancuso A, Toal GG, Tong L, Mosley A, Hsieh AL, Sullivan DK, et al. The MYC oncogene cooperates with sterol-regulated element-binding protein to regulate lipogenesis essential for neoplastic growth. Cell Metab. 2019;30(3):556-572 e555.PubMedPubMedCentral
84.
go back to reference Chen J, Ding C, Chen Y, Hu W, Yu C, Peng C, Feng X, Cheng Q, Wu W, Lu Y, et al. ACSL4 reprograms fatty acid metabolism in hepatocellular carcinoma via c-Myc/SREBP1 pathway. Cancer Lett. 2021;502:154–65.PubMed Chen J, Ding C, Chen Y, Hu W, Yu C, Peng C, Feng X, Cheng Q, Wu W, Lu Y, et al. ACSL4 reprograms fatty acid metabolism in hepatocellular carcinoma via c-Myc/SREBP1 pathway. Cancer Lett. 2021;502:154–65.PubMed
85.
go back to reference Jia J, Che L, Cigliano A, Wang X, Peitta G, Tao J, Zhong S, Ribback S, Evert M, Chen X, et al. Pivotal role of fatty acid synthase in c-MYC Driven Hepatocarcinogenesis. Int J Mol Sci. 2020;21(22):8467.PubMedPubMedCentral Jia J, Che L, Cigliano A, Wang X, Peitta G, Tao J, Zhong S, Ribback S, Evert M, Chen X, et al. Pivotal role of fatty acid synthase in c-MYC Driven Hepatocarcinogenesis. Int J Mol Sci. 2020;21(22):8467.PubMedPubMedCentral
86.
go back to reference Zhong C, Fan L, Yao F, Shi J, Fang W, Zhao H. HMGCR is necessary for the tumorigenecity of esophageal squamous cell carcinoma and is regulated by Myc. Tumour Biol. 2014;35(5):4123–9.PubMed Zhong C, Fan L, Yao F, Shi J, Fang W, Zhao H. HMGCR is necessary for the tumorigenecity of esophageal squamous cell carcinoma and is regulated by Myc. Tumour Biol. 2014;35(5):4123–9.PubMed
87.
go back to reference Zhong C, Fan L, Li Z, Yao F, Zhao H. SREBP2 is upregulated in esophageal squamous cell carcinoma and co-operates with c-Myc to regulate HMGCR expression. Mol Med Rep. 2019;20(4):3003–10.PubMedPubMedCentral Zhong C, Fan L, Li Z, Yao F, Zhao H. SREBP2 is upregulated in esophageal squamous cell carcinoma and co-operates with c-Myc to regulate HMGCR expression. Mol Med Rep. 2019;20(4):3003–10.PubMedPubMedCentral
88.
go back to reference Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK, Nissim I, Daikhin E, Yudkoff M, McMahon SB, et al. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci. 2008;105(48):18782–7.PubMedPubMedCentral Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK, Nissim I, Daikhin E, Yudkoff M, McMahon SB, et al. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci. 2008;105(48):18782–7.PubMedPubMedCentral
90.
go back to reference Camarda R, Zhou AY, Kohnz RA, Balakrishnan S, Mahieu C, Anderton B, Eyob H, Kajimura S, Tward A, Krings G, et al. Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer. Nat Med. 2016;22(4):427–32.PubMedPubMedCentral Camarda R, Zhou AY, Kohnz RA, Balakrishnan S, Mahieu C, Anderton B, Eyob H, Kajimura S, Tward A, Krings G, et al. Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer. Nat Med. 2016;22(4):427–32.PubMedPubMedCentral
91.
go back to reference Casciano JC, Perry C, Cohen-Nowak AJ, Miller KD, Vande Voorde J, Zhang Q, Chalmers S, Sandison ME, Liu Q, Hedley A, et al. MYC regulates fatty acid metabolism through a multigenic program in claudin-low triple negative breast cancer. Br J Cancer. 2020;122(6):868–84.PubMedPubMedCentral Casciano JC, Perry C, Cohen-Nowak AJ, Miller KD, Vande Voorde J, Zhang Q, Chalmers S, Sandison ME, Liu Q, Hedley A, et al. MYC regulates fatty acid metabolism through a multigenic program in claudin-low triple negative breast cancer. Br J Cancer. 2020;122(6):868–84.PubMedPubMedCentral
92.
go back to reference Hinshaw DC, Shevde LA. The tumor microenvironment innately modulates cancer progression. Cancer Res. 2019;79(18):4557–66.PubMedPubMedCentral Hinshaw DC, Shevde LA. The tumor microenvironment innately modulates cancer progression. Cancer Res. 2019;79(18):4557–66.PubMedPubMedCentral
93.
go back to reference Shao C, Yang F, Miao S, Liu W, Wang C, Shu Y, Shen H. Role of hypoxia-induced exosomes in tumor biology. Mol Cancer. 2018;17(1):120.PubMedPubMedCentral Shao C, Yang F, Miao S, Liu W, Wang C, Shu Y, Shen H. Role of hypoxia-induced exosomes in tumor biology. Mol Cancer. 2018;17(1):120.PubMedPubMedCentral
94.
go back to reference Munir R, Lisec J, Swinnen JV, Zaidi N. Lipid metabolism in cancer cells under metabolic stress. Br J Cancer. 2019;120(12):1090–8.PubMedPubMedCentral Munir R, Lisec J, Swinnen JV, Zaidi N. Lipid metabolism in cancer cells under metabolic stress. Br J Cancer. 2019;120(12):1090–8.PubMedPubMedCentral
95.
go back to reference Wise DR, Ward PS, Shay JE, Cross JR, Gruber JJ, Sachdeva UM, Platt JM, DeMatteo RG, Simon MC, Thompson CB. Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of alpha-ketoglutarate to citrate to support cell growth and viability. Proc Natl Acad Sci. 2011;108(49):19611–6.PubMedPubMedCentral Wise DR, Ward PS, Shay JE, Cross JR, Gruber JJ, Sachdeva UM, Platt JM, DeMatteo RG, Simon MC, Thompson CB. Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of alpha-ketoglutarate to citrate to support cell growth and viability. Proc Natl Acad Sci. 2011;108(49):19611–6.PubMedPubMedCentral
96.
go back to reference Metallo CM, Gameiro PA, Bell EL, Mattaini KR, Yang J, Hiller K, Jewell CM, Johnson ZR, Irvine DJ, Guarente L, et al. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature. 2011;481(7381):380–4.PubMedPubMedCentral Metallo CM, Gameiro PA, Bell EL, Mattaini KR, Yang J, Hiller K, Jewell CM, Johnson ZR, Irvine DJ, Guarente L, et al. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature. 2011;481(7381):380–4.PubMedPubMedCentral
97.
go back to reference Liu Y, Ma Z, Zhao C, Wang Y, Wu G, Xiao J, McClain CJ, Li X, Feng W. HIF-1alpha and HIF-2alpha are critically involved in hypoxia-induced lipid accumulation in hepatocytes through reducing PGC-1alpha-mediated fatty acid beta-oxidation. Toxicol Lett. 2014;226(2):117–23.PubMed Liu Y, Ma Z, Zhao C, Wang Y, Wu G, Xiao J, McClain CJ, Li X, Feng W. HIF-1alpha and HIF-2alpha are critically involved in hypoxia-induced lipid accumulation in hepatocytes through reducing PGC-1alpha-mediated fatty acid beta-oxidation. Toxicol Lett. 2014;226(2):117–23.PubMed
98.
go back to reference Ezzeddini R, Taghikhani M, Salek Farrokhi A, Somi MH, Samadi N, Esfahani A, Rasaee MJ. Downregulation of fatty acid oxidation by involvement of HIF-1alpha and PPARgamma in human gastric adenocarcinoma and related clinical significance. J Physiol Biochem. 2021;77(2):249–60.PubMed Ezzeddini R, Taghikhani M, Salek Farrokhi A, Somi MH, Samadi N, Esfahani A, Rasaee MJ. Downregulation of fatty acid oxidation by involvement of HIF-1alpha and PPARgamma in human gastric adenocarcinoma and related clinical significance. J Physiol Biochem. 2021;77(2):249–60.PubMed
99.
go back to reference Du W, Zhang L, Brett-Morris A, Aguila B, Kerner J, Hoppel CL, Puchowicz M, Serra D, Herrero L, Rini BI, et al. HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism. Nat Commun. 2017;8(1):1769.PubMedPubMedCentral Du W, Zhang L, Brett-Morris A, Aguila B, Kerner J, Hoppel CL, Puchowicz M, Serra D, Herrero L, Rini BI, et al. HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism. Nat Commun. 2017;8(1):1769.PubMedPubMedCentral
100.
go back to reference Seo J, Jeong DW, Park JW, Lee KW, Fukuda J, Chun YS. Fatty-acid-induced FABP5/HIF-1 reprograms lipid metabolism and enhances the proliferation of liver cancer cells. Commun Biol. 2020;3(1):638.PubMedPubMedCentral Seo J, Jeong DW, Park JW, Lee KW, Fukuda J, Chun YS. Fatty-acid-induced FABP5/HIF-1 reprograms lipid metabolism and enhances the proliferation of liver cancer cells. Commun Biol. 2020;3(1):638.PubMedPubMedCentral
101.
go back to reference Qiu B, Ackerman D, Sanchez DJ, Li B, Ochocki JD, Grazioli A, Bobrovnikova-Marjon E, Diehl JA, Keith B, Simon MC. HIF2alpha-dependent lipid storage promotes endoplasmic reticulum homeostasis in clear-cell renal cell carcinoma. Cancer Discov. 2015;5(6):652–67.PubMedPubMedCentral Qiu B, Ackerman D, Sanchez DJ, Li B, Ochocki JD, Grazioli A, Bobrovnikova-Marjon E, Diehl JA, Keith B, Simon MC. HIF2alpha-dependent lipid storage promotes endoplasmic reticulum homeostasis in clear-cell renal cell carcinoma. Cancer Discov. 2015;5(6):652–67.PubMedPubMedCentral
102.
go back to reference Kamphorst JJ, Cross JR, Fan J, de Stanchina E, Mathew R, White EP, Thompson CB, Rabinowitz JD. Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. Proc Natl Acad Sci. 2013;110(22):8882–7.PubMedPubMedCentral Kamphorst JJ, Cross JR, Fan J, de Stanchina E, Mathew R, White EP, Thompson CB, Rabinowitz JD. Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. Proc Natl Acad Sci. 2013;110(22):8882–7.PubMedPubMedCentral
103.
go back to reference Ackerman D, Tumanov S, Qiu B, Michalopoulou E, Spata M, Azzam A, Xie H, Simon MC, Kamphorst JJ. Triglycerides promote lipid homeostasis during hypoxic stress by balancing fatty acid saturation. Cell Rep. 2018;24(10):2596-2605 e2595.PubMedPubMedCentral Ackerman D, Tumanov S, Qiu B, Michalopoulou E, Spata M, Azzam A, Xie H, Simon MC, Kamphorst JJ. Triglycerides promote lipid homeostasis during hypoxic stress by balancing fatty acid saturation. Cell Rep. 2018;24(10):2596-2605 e2595.PubMedPubMedCentral
104.
go back to reference Mylonis I, Simos G, Paraskeva E. Hypoxia-inducible factors and the regulation of lipid metabolism. Cells. 2019;8(3):214.PubMedPubMedCentral Mylonis I, Simos G, Paraskeva E. Hypoxia-inducible factors and the regulation of lipid metabolism. Cells. 2019;8(3):214.PubMedPubMedCentral
105.
go back to reference Boedtkjer E, Pedersen SF. The acidic tumor microenvironment as a driver of cancer. Annu Rev Physiol. 2020;82:103–26.PubMed Boedtkjer E, Pedersen SF. The acidic tumor microenvironment as a driver of cancer. Annu Rev Physiol. 2020;82:103–26.PubMed
106.
go back to reference Maan M, Peters JM, Dutta M, Patterson AD. Lipid metabolism and lipophagy in cancer. Biochem Biophys Res Commun. 2018;504(3):582–9.PubMedPubMedCentral Maan M, Peters JM, Dutta M, Patterson AD. Lipid metabolism and lipophagy in cancer. Biochem Biophys Res Commun. 2018;504(3):582–9.PubMedPubMedCentral
107.
go back to reference Corbet C, Bastien E, Santiago de Jesus JP, Dierge E, Martherus R, Vander Linden C, Doix B, Degavre C, Guilbaud C, Petit L, et al. TGFbeta2-induced formation of lipid droplets supports acidosis-driven EMT and the metastatic spreading of cancer cells. Nat Commun. 2020;11(1):454.PubMedPubMedCentral Corbet C, Bastien E, Santiago de Jesus JP, Dierge E, Martherus R, Vander Linden C, Doix B, Degavre C, Guilbaud C, Petit L, et al. TGFbeta2-induced formation of lipid droplets supports acidosis-driven EMT and the metastatic spreading of cancer cells. Nat Commun. 2020;11(1):454.PubMedPubMedCentral
108.
go back to reference Ding M, Zhang S, Guo Y, Yao J, Shen Q, Huang M, Chen W, Yu S, Zheng Y, Lin Y, et al. Tumor microenvironment acidity triggers lipid accumulation in liver cancer via scd1 activation. Mol Cancer Res. 2022;20(5):810–22.PubMed Ding M, Zhang S, Guo Y, Yao J, Shen Q, Huang M, Chen W, Yu S, Zheng Y, Lin Y, et al. Tumor microenvironment acidity triggers lipid accumulation in liver cancer via scd1 activation. Mol Cancer Res. 2022;20(5):810–22.PubMed
109.
go back to reference Kondo A, Yamamoto S, Nakaki R, Shimamura T, Hamakubo T, Sakai J, Kodama T, Yoshida T, Aburatani H, Osawa T. Extracellular acidic pH activates the sterol regulatory element-binding protein 2 to promote tumor progression. Cell Rep. 2017;18(9):2228–42.PubMed Kondo A, Yamamoto S, Nakaki R, Shimamura T, Hamakubo T, Sakai J, Kodama T, Yoshida T, Aburatani H, Osawa T. Extracellular acidic pH activates the sterol regulatory element-binding protein 2 to promote tumor progression. Cell Rep. 2017;18(9):2228–42.PubMed
110.
go back to reference Vaupel P, Kallinowski F, Okunieff P. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res. 1989;49(23):6449–65.PubMed Vaupel P, Kallinowski F, Okunieff P. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res. 1989;49(23):6449–65.PubMed
111.
go back to reference Quail DF, Dannenberg AJ. The obese adipose tissue microenvironment in cancer development and progression. Nat Rev Endocrinol. 2019;15(3):139–54.PubMedPubMedCentral Quail DF, Dannenberg AJ. The obese adipose tissue microenvironment in cancer development and progression. Nat Rev Endocrinol. 2019;15(3):139–54.PubMedPubMedCentral
112.
go back to reference Wu Q, Li B, Li Z, Li J, Sun S, Sun S. Cancer-associated adipocytes: key players in breast cancer progression. J Hematol Oncol. 2019;12(1):95.PubMedPubMedCentral Wu Q, Li B, Li Z, Li J, Sun S, Sun S. Cancer-associated adipocytes: key players in breast cancer progression. J Hematol Oncol. 2019;12(1):95.PubMedPubMedCentral
113.
go back to reference Yang D, Li Y, Xing L, Tan Y, Sun J, Zeng B, Xiang T, Tan J, Ren G, Wang Y. Utilization of adipocyte-derived lipids and enhanced intracellular trafficking of fatty acids contribute to breast cancer progression. Cell Commun Signal. 2018;16(1):32.PubMedPubMedCentral Yang D, Li Y, Xing L, Tan Y, Sun J, Zeng B, Xiang T, Tan J, Ren G, Wang Y. Utilization of adipocyte-derived lipids and enhanced intracellular trafficking of fatty acids contribute to breast cancer progression. Cell Commun Signal. 2018;16(1):32.PubMedPubMedCentral
114.
go back to reference Attane C, Muller C. Drilling for oil: tumor-surrounding adipocytes fueling cancer. Trends Cancer. 2020;6(7):593–604.PubMed Attane C, Muller C. Drilling for oil: tumor-surrounding adipocytes fueling cancer. Trends Cancer. 2020;6(7):593–604.PubMed
115.
go back to reference Corn KC, Windham MA, Rafat M. Lipids in the tumor microenvironment: from cancer progression to treatment. Prog Lipid Res. 2020;80: 101055.PubMedPubMedCentral Corn KC, Windham MA, Rafat M. Lipids in the tumor microenvironment: from cancer progression to treatment. Prog Lipid Res. 2020;80: 101055.PubMedPubMedCentral
116.
go back to reference Tabuso M, Homer-Vanniasinkam S, Adya R, Arasaradnam RP. Role of tissue microenvironment resident adipocytes in colon cancer. World J Gastroenterol. 2017;23(32):5829–35.PubMedPubMedCentral Tabuso M, Homer-Vanniasinkam S, Adya R, Arasaradnam RP. Role of tissue microenvironment resident adipocytes in colon cancer. World J Gastroenterol. 2017;23(32):5829–35.PubMedPubMedCentral
117.
go back to reference Balaban S, Shearer RF, Lee LS, van Geldermalsen M, Schreuder M, Shtein HC, Cairns R, Thomas KC, Fazakerley DJ, Grewal T, et al. Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration. Cancer Metab. 2017;5:1.PubMedPubMedCentral Balaban S, Shearer RF, Lee LS, van Geldermalsen M, Schreuder M, Shtein HC, Cairns R, Thomas KC, Fazakerley DJ, Grewal T, et al. Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration. Cancer Metab. 2017;5:1.PubMedPubMedCentral
118.
go back to reference Lien EC, Vander Heiden MG. A framework for examining how diet impacts tumour metabolism. Nat Rev Cancer. 2019;19(11):651–61.PubMed Lien EC, Vander Heiden MG. A framework for examining how diet impacts tumour metabolism. Nat Rev Cancer. 2019;19(11):651–61.PubMed
119.
go back to reference Petrelli F, Cortellini A, Indini A, Tomasello G, Ghidini M, Nigro O, Salati M, Dottorini L, Iaculli A, Varricchio A, et al. Association of obesity with survival outcomes in patients with cancer: a systematic review and meta-analysis. JAMA Netw Open. 2021;4(3): e213520.PubMedPubMedCentral Petrelli F, Cortellini A, Indini A, Tomasello G, Ghidini M, Nigro O, Salati M, Dottorini L, Iaculli A, Varricchio A, et al. Association of obesity with survival outcomes in patients with cancer: a systematic review and meta-analysis. JAMA Netw Open. 2021;4(3): e213520.PubMedPubMedCentral
120.
go back to reference Deng T, Lyon CJ, Bergin S, Caligiuri MA, Hsueh WA. Obesity, inflammation, and cancer. Annu Rev Pathol. 2016;11:421–49.PubMed Deng T, Lyon CJ, Bergin S, Caligiuri MA, Hsueh WA. Obesity, inflammation, and cancer. Annu Rev Pathol. 2016;11:421–49.PubMed
121.
go back to reference Beyaz S, Mana MD, Roper J, Kedrin D, Saadatpour A, Hong SJ, Bauer-Rowe KE, Xifaras ME, Akkad A, Arias E, et al. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature. 2016;531(7592):53–8.PubMedPubMedCentral Beyaz S, Mana MD, Roper J, Kedrin D, Saadatpour A, Hong SJ, Bauer-Rowe KE, Xifaras ME, Akkad A, Arias E, et al. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature. 2016;531(7592):53–8.PubMedPubMedCentral
122.
go back to reference Kulkarni A, Bowers LW. The role of immune dysfunction in obesity-associated cancer risk, progression, and metastasis. Cell Mol Life Sci. 2021;78(7):3423–42.PubMed Kulkarni A, Bowers LW. The role of immune dysfunction in obesity-associated cancer risk, progression, and metastasis. Cell Mol Life Sci. 2021;78(7):3423–42.PubMed
123.
go back to reference Kado T, Nawaz A, Takikawa A, Usui I, Tobe K. Linkage of CD8(+) T cell exhaustion with high-fat diet-induced tumourigenesis. Sci Rep. 2019;9(1):12284.PubMedPubMedCentral Kado T, Nawaz A, Takikawa A, Usui I, Tobe K. Linkage of CD8(+) T cell exhaustion with high-fat diet-induced tumourigenesis. Sci Rep. 2019;9(1):12284.PubMedPubMedCentral
124.
go back to reference Wang Z, Aguilar EG, Luna JI, Dunai C, Khuat LT, Le CT, Mirsoian A, Minnar CM, Stoffel KM, Sturgill IR, et al. Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade. Nat Med. 2019;25(1):141–51.PubMed Wang Z, Aguilar EG, Luna JI, Dunai C, Khuat LT, Le CT, Mirsoian A, Minnar CM, Stoffel KM, Sturgill IR, et al. Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade. Nat Med. 2019;25(1):141–51.PubMed
125.
go back to reference Chen M, Zhang J, Sampieri K, Clohessy JG, Mendez L, Gonzalez-Billalabeitia E, Liu XS, Lee YR, Fung J, Katon JM, et al. An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer. Nat Genet. 2018;50(2):206–18.PubMedPubMedCentral Chen M, Zhang J, Sampieri K, Clohessy JG, Mendez L, Gonzalez-Billalabeitia E, Liu XS, Lee YR, Fung J, Katon JM, et al. An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer. Nat Genet. 2018;50(2):206–18.PubMedPubMedCentral
126.
go back to reference Bousquenaud M, Fico F, Solinas G, Ruegg C, Santamaria-Martinez A. Obesity promotes the expansion of metastasis-initiating cells in breast cancer. Breast Cancer Res. 2018;20(1):104.PubMedPubMedCentral Bousquenaud M, Fico F, Solinas G, Ruegg C, Santamaria-Martinez A. Obesity promotes the expansion of metastasis-initiating cells in breast cancer. Breast Cancer Res. 2018;20(1):104.PubMedPubMedCentral
127.
go back to reference Pascual G, Dominguez D, Elosua-Bayes M, Beckedorff F, Laudanna C, Bigas C, Douillet D, Greco C, Symeonidi A, Hernandez I, et al. Dietary palmitic acid promotes a prometastatic memory via Schwann cells. Nature. 2021;599(7885):485–90.PubMed Pascual G, Dominguez D, Elosua-Bayes M, Beckedorff F, Laudanna C, Bigas C, Douillet D, Greco C, Symeonidi A, Hernandez I, et al. Dietary palmitic acid promotes a prometastatic memory via Schwann cells. Nature. 2021;599(7885):485–90.PubMed
128.
go back to reference Labbe DP, Zadra G, Yang M, Reyes JM, Lin CY, Cacciatore S, Ebot EM, Creech AL, Giunchi F, Fiorentino M, et al. High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program. Nat Commun. 2019;10(1):4358.PubMedPubMedCentral Labbe DP, Zadra G, Yang M, Reyes JM, Lin CY, Cacciatore S, Ebot EM, Creech AL, Giunchi F, Fiorentino M, et al. High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program. Nat Commun. 2019;10(1):4358.PubMedPubMedCentral
129.
go back to reference Li S, Wu T, Lu YX, Wang JX, Yu FH, Yang MZ, Huang YJ, Li ZJ, Wang SL, Huang L, et al. Obesity promotes gastric cancer metastasis via diacylglycerol acyltransferase 2-dependent lipid droplets accumulation and redox homeostasis. Redox Biol. 2020;36: 101596.PubMedPubMedCentral Li S, Wu T, Lu YX, Wang JX, Yu FH, Yang MZ, Huang YJ, Li ZJ, Wang SL, Huang L, et al. Obesity promotes gastric cancer metastasis via diacylglycerol acyltransferase 2-dependent lipid droplets accumulation and redox homeostasis. Redox Biol. 2020;36: 101596.PubMedPubMedCentral
130.
go back to reference Tutino V, De Nunzio V, Caruso MG, Veronese N, Lorusso D, Di Masi M, Benedetto ML, Notarnicola M. Elevated AA/EPA ratio represents an inflammatory biomarker in tumor tissue of metastatic colorectal cancer patients. Int J Mol Sci. 2019;20(8):2050.PubMedPubMedCentral Tutino V, De Nunzio V, Caruso MG, Veronese N, Lorusso D, Di Masi M, Benedetto ML, Notarnicola M. Elevated AA/EPA ratio represents an inflammatory biomarker in tumor tissue of metastatic colorectal cancer patients. Int J Mol Sci. 2019;20(8):2050.PubMedPubMedCentral
131.
go back to reference Matsuoka T, Adair JE, Lih FB, Hsi LC, Rubino M, Eling TE, Tomer KB, Yashiro M, Hirakawa K, Olden K, et al. Elevated dietary linoleic acid increases gastric carcinoma cell invasion and metastasis in mice. Br J Cancer. 2010;103(8):1182–91.PubMedPubMedCentral Matsuoka T, Adair JE, Lih FB, Hsi LC, Rubino M, Eling TE, Tomer KB, Yashiro M, Hirakawa K, Olden K, et al. Elevated dietary linoleic acid increases gastric carcinoma cell invasion and metastasis in mice. Br J Cancer. 2010;103(8):1182–91.PubMedPubMedCentral
132.
go back to reference Chen X, Song E. Turning foes to friends: targeting cancer-associated fibroblasts. Nat Rev Drug Discov. 2019;18(2):99–115.PubMed Chen X, Song E. Turning foes to friends: targeting cancer-associated fibroblasts. Nat Rev Drug Discov. 2019;18(2):99–115.PubMed
133.
go back to reference Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer. 2016;16(9):582–98.PubMed Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer. 2016;16(9):582–98.PubMed
134.
go back to reference Sahai E, Astsaturov I, Cukierman E, DeNardo DG, Egeblad M, Evans RM, Fearon D, Greten FR, Hingorani SR, Hunter T, et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat Rev Cancer. 2020;20(3):174–86.PubMedPubMedCentral Sahai E, Astsaturov I, Cukierman E, DeNardo DG, Egeblad M, Evans RM, Fearon D, Greten FR, Hingorani SR, Hunter T, et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat Rev Cancer. 2020;20(3):174–86.PubMedPubMedCentral
135.
go back to reference Gong J, Lin Y, Zhang H, Liu C, Cheng Z, Yang X, Zhang J, Xiao Y, Sang N, Qian X, et al. Reprogramming of lipid metabolism in cancer-associated fibroblasts potentiates migration of colorectal cancer cells. Cell Death Dis. 2020;11(4):267.PubMedPubMedCentral Gong J, Lin Y, Zhang H, Liu C, Cheng Z, Yang X, Zhang J, Xiao Y, Sang N, Qian X, et al. Reprogramming of lipid metabolism in cancer-associated fibroblasts potentiates migration of colorectal cancer cells. Cell Death Dis. 2020;11(4):267.PubMedPubMedCentral
136.
go back to reference Zhang Y, Gu Z, Wan J, Lou X, Liu S, Wang Y, Bian Y, Wang F, Li Z, Qin Z. Stearoyl-CoA Desaturase-1 dependent lipid droplets accumulation in cancer-associated fibroblasts facilitates the progression of lung cancer. Int J Biol Sci. 2022;18(16):6114–28.PubMedPubMedCentral Zhang Y, Gu Z, Wan J, Lou X, Liu S, Wang Y, Bian Y, Wang F, Li Z, Qin Z. Stearoyl-CoA Desaturase-1 dependent lipid droplets accumulation in cancer-associated fibroblasts facilitates the progression of lung cancer. Int J Biol Sci. 2022;18(16):6114–28.PubMedPubMedCentral
137.
go back to reference Nardi F, Fitchev P, Franco OE, Ivanisevic J, Scheibler A, Hayward SW, Brendler CB, Welte MA, Crawford SE. PEDF regulates plasticity of a novel lipid-MTOC axis in prostate cancer-associated fibroblasts. J Cell Sci. 2018;131(13):jcs213579.PubMedPubMedCentral Nardi F, Fitchev P, Franco OE, Ivanisevic J, Scheibler A, Hayward SW, Brendler CB, Welte MA, Crawford SE. PEDF regulates plasticity of a novel lipid-MTOC axis in prostate cancer-associated fibroblasts. J Cell Sci. 2018;131(13):jcs213579.PubMedPubMedCentral
138.
go back to reference Hwang SH, Yang Y, Jung JH, Kim Y. Oleic acid from cancer-associated fibroblast promotes cancer cell stemness by stearoyl-CoA desaturase under glucose-deficient condition. Cancer Cell Int. 2022;22(1):404.PubMedPubMedCentral Hwang SH, Yang Y, Jung JH, Kim Y. Oleic acid from cancer-associated fibroblast promotes cancer cell stemness by stearoyl-CoA desaturase under glucose-deficient condition. Cancer Cell Int. 2022;22(1):404.PubMedPubMedCentral
139.
go back to reference Peng S, Li Y, Huang M, Tang G, Xie Y, Chen D, Hu Y, Yu T, Cai J, Yuan Z, et al. Metabolomics reveals that CAF-derived lipids promote colorectal cancer peritoneal metastasis by enhancing membrane fluidity. Int J Biol Sci. 2022;18(5):1912–32.PubMedPubMedCentral Peng S, Li Y, Huang M, Tang G, Xie Y, Chen D, Hu Y, Yu T, Cai J, Yuan Z, et al. Metabolomics reveals that CAF-derived lipids promote colorectal cancer peritoneal metastasis by enhancing membrane fluidity. Int J Biol Sci. 2022;18(5):1912–32.PubMedPubMedCentral
140.
go back to reference Peng S, Chen D, Cai J, Yuan Z, Huang B, Li Y, Wang H, Luo Q, Kuang Y, Liang W, et al. Enhancing cancer-associated fibroblast fatty acid catabolism within a metabolically challenging tumor microenvironment drives colon cancer peritoneal metastasis. Mol Oncol. 2021;15(5):1391–411.PubMedPubMedCentral Peng S, Chen D, Cai J, Yuan Z, Huang B, Li Y, Wang H, Luo Q, Kuang Y, Liang W, et al. Enhancing cancer-associated fibroblast fatty acid catabolism within a metabolically challenging tumor microenvironment drives colon cancer peritoneal metastasis. Mol Oncol. 2021;15(5):1391–411.PubMedPubMedCentral
141.
go back to reference Li C, Teixeira AF, Zhu HJ, Ten Dijke P. Cancer associated-fibroblast-derived exosomes in cancer progression. Mol Cancer. 2021;20(1):154.PubMedPubMedCentral Li C, Teixeira AF, Zhu HJ, Ten Dijke P. Cancer associated-fibroblast-derived exosomes in cancer progression. Mol Cancer. 2021;20(1):154.PubMedPubMedCentral
142.
go back to reference Li Z, Sun C, Qin Z. Metabolic reprogramming of cancer-associated fibroblasts and its effect on cancer cell reprogramming. Theranostics. 2021;11(17):8322–36.PubMedPubMedCentral Li Z, Sun C, Qin Z. Metabolic reprogramming of cancer-associated fibroblasts and its effect on cancer cell reprogramming. Theranostics. 2021;11(17):8322–36.PubMedPubMedCentral
143.
go back to reference Radhakrishnan R, Ha JH, Jayaraman M, Liu J, Moxley KM, Isidoro C, Sood AK, Song YS, Dhanasekaran DN. Ovarian cancer cell-derived lysophosphatidic acid induces glycolytic shift and cancer-associated fibroblast-phenotype in normal and peritumoral fibroblasts. Cancer Lett. 2019;442:464–74.PubMed Radhakrishnan R, Ha JH, Jayaraman M, Liu J, Moxley KM, Isidoro C, Sood AK, Song YS, Dhanasekaran DN. Ovarian cancer cell-derived lysophosphatidic acid induces glycolytic shift and cancer-associated fibroblast-phenotype in normal and peritumoral fibroblasts. Cancer Lett. 2019;442:464–74.PubMed
144.
go back to reference Auciello FR, Bulusu V, Oon C, Tait-Mulder J, Berry M, Bhattacharyya S, Tumanov S, Allen-Petersen BL, Link J, Kendsersky ND, et al. A stromal lysolipid-autotaxin signaling axis promotes pancreatic tumor progression. Cancer Discov. 2019;9(5):617–27.PubMedPubMedCentral Auciello FR, Bulusu V, Oon C, Tait-Mulder J, Berry M, Bhattacharyya S, Tumanov S, Allen-Petersen BL, Link J, Kendsersky ND, et al. A stromal lysolipid-autotaxin signaling axis promotes pancreatic tumor progression. Cancer Discov. 2019;9(5):617–27.PubMedPubMedCentral
145.
go back to reference Kock A, Larsson K, Bergqvist F, Eissler N, Elfman LHM, Raouf J, Korotkova M, Johnsen JI, Jakobsson PJ, Kogner P. Inhibition of microsomal prostaglandin E synthase-1 in cancer-associated fibroblasts suppresses neuroblastoma tumor growth. EBioMedicine. 2018;32:84–92.PubMedPubMedCentral Kock A, Larsson K, Bergqvist F, Eissler N, Elfman LHM, Raouf J, Korotkova M, Johnsen JI, Jakobsson PJ, Kogner P. Inhibition of microsomal prostaglandin E synthase-1 in cancer-associated fibroblasts suppresses neuroblastoma tumor growth. EBioMedicine. 2018;32:84–92.PubMedPubMedCentral
146.
go back to reference Elwakeel E, Bruggemann M, Wagih J, Lityagina O, Elewa MAF, Han Y, Fromel T, Popp R, Nicolas AM, Schreiber Y, et al. Disruption of prostaglandin E2 signaling in cancer-associated fibroblasts limits mammary carcinoma growth but promotes metastasis. Cancer Res. 2022;82(7):1380–95.PubMed Elwakeel E, Bruggemann M, Wagih J, Lityagina O, Elewa MAF, Han Y, Fromel T, Popp R, Nicolas AM, Schreiber Y, et al. Disruption of prostaglandin E2 signaling in cancer-associated fibroblasts limits mammary carcinoma growth but promotes metastasis. Cancer Res. 2022;82(7):1380–95.PubMed
147.
go back to reference Weigel C, Maczis MA, Palladino END, Green CD, Maceyka M, Guo C, Wang XY, Dozmorov MG, Milstien S, Spiegel S. Sphingosine kinase 2 in stromal fibroblasts creates a hospitable tumor microenvironment in breast cancer. Cancer Res. 2023;83(4):553–67.PubMedPubMedCentral Weigel C, Maczis MA, Palladino END, Green CD, Maceyka M, Guo C, Wang XY, Dozmorov MG, Milstien S, Spiegel S. Sphingosine kinase 2 in stromal fibroblasts creates a hospitable tumor microenvironment in breast cancer. Cancer Res. 2023;83(4):553–67.PubMedPubMedCentral
148.
go back to reference Neuwirt H, Bouchal J, Kharaishvili G, Ploner C, Johrer K, Pitterl F, Weber A, Klocker H, Eder IE. Cancer-associated fibroblasts promote prostate tumor growth and progression through upregulation of cholesterol and steroid biosynthesis. Cell Commun Signal. 2020;18(1):11.PubMedPubMedCentral Neuwirt H, Bouchal J, Kharaishvili G, Ploner C, Johrer K, Pitterl F, Weber A, Klocker H, Eder IE. Cancer-associated fibroblasts promote prostate tumor growth and progression through upregulation of cholesterol and steroid biosynthesis. Cell Commun Signal. 2020;18(1):11.PubMedPubMedCentral
149.
go back to reference Zhang H, Deng T, Liu R, Ning T, Yang H, Liu D, Zhang Q, Lin D, Ge S, Bai M, et al. CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer. Mol Cancer. 2020;19(1):43.PubMedPubMedCentral Zhang H, Deng T, Liu R, Ning T, Yang H, Liu D, Zhang Q, Lin D, Ge S, Bai M, et al. CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer. Mol Cancer. 2020;19(1):43.PubMedPubMedCentral
150.
go back to reference Santi A, Caselli A, Ranaldi F, Paoli P, Mugnaioni C, Michelucci E, Cirri P. Cancer associated fibroblasts transfer lipids and proteins to cancer cells through cargo vesicles supporting tumor growth. Biochim Biophys Acta. 2015;1853(12):3211–23.PubMed Santi A, Caselli A, Ranaldi F, Paoli P, Mugnaioni C, Michelucci E, Cirri P. Cancer associated fibroblasts transfer lipids and proteins to cancer cells through cargo vesicles supporting tumor growth. Biochim Biophys Acta. 2015;1853(12):3211–23.PubMed
151.
go back to reference Lopes-Coelho F, Andre S, Felix A, Serpa J. Breast cancer metabolic cross-talk: fibroblasts are hubs and breast cancer cells are gatherers of lipids. Mol Cell Endocrinol. 2018;462(Pt B):93–106.PubMed Lopes-Coelho F, Andre S, Felix A, Serpa J. Breast cancer metabolic cross-talk: fibroblasts are hubs and breast cancer cells are gatherers of lipids. Mol Cell Endocrinol. 2018;462(Pt B):93–106.PubMed
152.
go back to reference Zhao H, Yang L, Baddour J, Achreja A, Bernard V, Moss T, Marini JC, Tudawe T, Seviour EG, San Lucas FA, et al. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism. Elife. 2016;5: e10250.PubMedPubMedCentral Zhao H, Yang L, Baddour J, Achreja A, Bernard V, Moss T, Marini JC, Tudawe T, Seviour EG, San Lucas FA, et al. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism. Elife. 2016;5: e10250.PubMedPubMedCentral
153.
go back to reference Zhu GQ, Tang Z, Huang R, Qu WF, Fang Y, Yang R, Tao CY, Gao J, Wu XL, Sun HX, et al. CD36(+) cancer-associated fibroblasts provide immunosuppressive microenvironment for hepatocellular carcinoma via secretion of macrophage migration inhibitory factor. Cell Discov. 2023;9(1):25.PubMedPubMedCentral Zhu GQ, Tang Z, Huang R, Qu WF, Fang Y, Yang R, Tao CY, Gao J, Wu XL, Sun HX, et al. CD36(+) cancer-associated fibroblasts provide immunosuppressive microenvironment for hepatocellular carcinoma via secretion of macrophage migration inhibitory factor. Cell Discov. 2023;9(1):25.PubMedPubMedCentral
154.
go back to reference Chang CH, Qiu J, O’Sullivan D, Buck MD, Noguchi T, Curtis JD, Chen Q, Gindin M, Gubin MM, van der Windt GJ, et al. Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell. 2015;162(6):1229–41.PubMedPubMedCentral Chang CH, Qiu J, O’Sullivan D, Buck MD, Noguchi T, Curtis JD, Chen Q, Gindin M, Gubin MM, van der Windt GJ, et al. Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell. 2015;162(6):1229–41.PubMedPubMedCentral
155.
go back to reference Luo Q, Zheng N, Jiang L, Wang T, Zhang P, Liu Y, Zheng P, Wang W, Xie G, Chen L, et al. Lipid accumulation in macrophages confers protumorigenic polarization and immunity in gastric cancer. Cancer Sci. 2020;111(11):4000–11.PubMedPubMedCentral Luo Q, Zheng N, Jiang L, Wang T, Zhang P, Liu Y, Zheng P, Wang W, Xie G, Chen L, et al. Lipid accumulation in macrophages confers protumorigenic polarization and immunity in gastric cancer. Cancer Sci. 2020;111(11):4000–11.PubMedPubMedCentral
156.
go back to reference Fridman WH, Pages F, Sautes-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12(4):298–306.PubMed Fridman WH, Pages F, Sautes-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12(4):298–306.PubMed
157.
go back to reference Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568–71.PubMedPubMedCentral Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568–71.PubMedPubMedCentral
161.
go back to reference Ma X, Bi E, Lu Y, Su P, Huang C, Liu L, Wang Q, Yang M, Kalady MF, Qian J, et al. Cholesterol induces CD8(+) T cell exhaustion in the tumor microenvironment. Cell Metab. 2019;30(1):143-156 e145.PubMedPubMedCentral Ma X, Bi E, Lu Y, Su P, Huang C, Liu L, Wang Q, Yang M, Kalady MF, Qian J, et al. Cholesterol induces CD8(+) T cell exhaustion in the tumor microenvironment. Cell Metab. 2019;30(1):143-156 e145.PubMedPubMedCentral
162.
go back to reference Zhang C, Yue C, Herrmann A, Song J, Egelston C, Wang T, Zhang Z, Li W, Lee H, Aftabizadeh M, et al. STAT3 activation-induced fatty acid oxidation in CD8(+) T effector cells is critical for obesity-promoted breast tumor growth. Cell Metab. 2020;31(1):148-161 e145.PubMed Zhang C, Yue C, Herrmann A, Song J, Egelston C, Wang T, Zhang Z, Li W, Lee H, Aftabizadeh M, et al. STAT3 activation-induced fatty acid oxidation in CD8(+) T effector cells is critical for obesity-promoted breast tumor growth. Cell Metab. 2020;31(1):148-161 e145.PubMed
163.
go back to reference Zhang Y, Kurupati R, Liu L, Zhou XY, Zhang G, Hudaihed A, Filisio F, Giles-Davis W, Xu X, Karakousis GC, et al. Enhancing CD8(+) T cell fatty acid catabolism within a metabolically challenging tumor microenvironment increases the efficacy of melanoma immunotherapy. Cancer Cell. 2017;32(3):377-391 e379.PubMedPubMedCentral Zhang Y, Kurupati R, Liu L, Zhou XY, Zhang G, Hudaihed A, Filisio F, Giles-Davis W, Xu X, Karakousis GC, et al. Enhancing CD8(+) T cell fatty acid catabolism within a metabolically challenging tumor microenvironment increases the efficacy of melanoma immunotherapy. Cancer Cell. 2017;32(3):377-391 e379.PubMedPubMedCentral
164.
go back to reference Chowdhury PS, Chamoto K, Kumar A, Honjo T. PPAR-induced fatty acid oxidation in t cells increases the number of tumor-reactive CD8(+) T Cells and facilitates anti-PD-1 therapy. Cancer Immunol Res. 2018;6(11):1375–87.PubMed Chowdhury PS, Chamoto K, Kumar A, Honjo T. PPAR-induced fatty acid oxidation in t cells increases the number of tumor-reactive CD8(+) T Cells and facilitates anti-PD-1 therapy. Cancer Immunol Res. 2018;6(11):1375–87.PubMed
166.
go back to reference Patsoukis N, Bardhan K, Chatterjee P, Sari D, Liu B, Bell LN, Karoly ED, Freeman GJ, Petkova V, Seth P, et al. PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation. Nat Commun. 2015;6:6692.PubMed Patsoukis N, Bardhan K, Chatterjee P, Sari D, Liu B, Bell LN, Karoly ED, Freeman GJ, Petkova V, Seth P, et al. PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation. Nat Commun. 2015;6:6692.PubMed
167.
go back to reference Ringel AE, Drijvers JM, Baker GJ, Catozzi A, Garcia-Canaveras JC, Gassaway BM, Miller BC, Juneja VR, Nguyen TH, Joshi S, et al. Obesity shapes metabolism in the tumor microenvironment to suppress anti-tumor immunity. Cell. 2020;183(7):1848-1866 e1826.PubMedPubMedCentral Ringel AE, Drijvers JM, Baker GJ, Catozzi A, Garcia-Canaveras JC, Gassaway BM, Miller BC, Juneja VR, Nguyen TH, Joshi S, et al. Obesity shapes metabolism in the tumor microenvironment to suppress anti-tumor immunity. Cell. 2020;183(7):1848-1866 e1826.PubMedPubMedCentral
168.
go back to reference Lin R, Zhang H, Yuan Y, He Q, Zhou J, Li S, Sun Y, Li DY, Qiu HB, Wang W, et al. Fatty acid oxidation controls CD8(+) tissue-resident memory T-cell survival in gastric adenocarcinoma. Cancer Immunol Res. 2020;8(4):479–92.PubMed Lin R, Zhang H, Yuan Y, He Q, Zhou J, Li S, Sun Y, Li DY, Qiu HB, Wang W, et al. Fatty acid oxidation controls CD8(+) tissue-resident memory T-cell survival in gastric adenocarcinoma. Cancer Immunol Res. 2020;8(4):479–92.PubMed
169.
go back to reference Ma X, Xiao L, Liu L, Ye L, Su P, Bi E, Wang Q, Yang M, Qian J, Yi Q. CD36-mediated ferroptosis dampens intratumoral CD8(+) T cell effector function and impairs their antitumor ability. Cell Metab. 2021;33(5):1001-1012 e1005.PubMedPubMedCentral Ma X, Xiao L, Liu L, Ye L, Su P, Bi E, Wang Q, Yang M, Qian J, Yi Q. CD36-mediated ferroptosis dampens intratumoral CD8(+) T cell effector function and impairs their antitumor ability. Cell Metab. 2021;33(5):1001-1012 e1005.PubMedPubMedCentral
171.
go back to reference Ma X, Bi E, Huang C, Lu Y, Xue G, Guo X, Wang A, Yang M, Qian J, Dong C, et al. Cholesterol negatively regulates IL-9-producing CD8(+) T cell differentiation and antitumor activity. J Exp Med. 2018;215(6):1555–69.PubMedPubMedCentral Ma X, Bi E, Huang C, Lu Y, Xue G, Guo X, Wang A, Yang M, Qian J, Dong C, et al. Cholesterol negatively regulates IL-9-producing CD8(+) T cell differentiation and antitumor activity. J Exp Med. 2018;215(6):1555–69.PubMedPubMedCentral
172.
go back to reference Yang W, Bai Y, Xiong Y, Zhang J, Chen S, Zheng X, Meng X, Li L, Wang J, Xu C, et al. Potentiating the antitumour response of CD8(+) T cells by modulating cholesterol metabolism. Nature. 2016;531(7596):651–5.PubMedPubMedCentral Yang W, Bai Y, Xiong Y, Zhang J, Chen S, Zheng X, Meng X, Li L, Wang J, Xu C, et al. Potentiating the antitumour response of CD8(+) T cells by modulating cholesterol metabolism. Nature. 2016;531(7596):651–5.PubMedPubMedCentral
173.
go back to reference Yan Y, Huang L, Liu Y, Yi M, Chu Q, Jiao D, Wu K. Metabolic profiles of regulatory T cells and their adaptations to the tumor microenvironment: implications for antitumor immunity. J Hematol Oncol. 2022;15(1):104.PubMedPubMedCentral Yan Y, Huang L, Liu Y, Yi M, Chu Q, Jiao D, Wu K. Metabolic profiles of regulatory T cells and their adaptations to the tumor microenvironment: implications for antitumor immunity. J Hematol Oncol. 2022;15(1):104.PubMedPubMedCentral
174.
go back to reference Wang H, Franco F, Ho PC. Metabolic regulation of tregs in cancer: opportunities for immunotherapy. Trends Cancer. 2017;3(8):583–92.PubMed Wang H, Franco F, Ho PC. Metabolic regulation of tregs in cancer: opportunities for immunotherapy. Trends Cancer. 2017;3(8):583–92.PubMed
175.
go back to reference Miska J, Lee-Chang C, Rashidi A, Muroski ME, Chang AL, Lopez-Rosas A, Zhang P, Panek WK, Cordero A, Han Y, et al. HIF-1alpha is a metabolic switch between glycolytic-driven migration and oxidative phosphorylation-driven immunosuppression of tregs in glioblastoma. Cell Rep. 2019;27(1):226-237 e224.PubMedPubMedCentral Miska J, Lee-Chang C, Rashidi A, Muroski ME, Chang AL, Lopez-Rosas A, Zhang P, Panek WK, Cordero A, Han Y, et al. HIF-1alpha is a metabolic switch between glycolytic-driven migration and oxidative phosphorylation-driven immunosuppression of tregs in glioblastoma. Cell Rep. 2019;27(1):226-237 e224.PubMedPubMedCentral
176.
go back to reference Lim SA, Wei J, Nguyen TM, Shi H, Su W, Palacios G, Dhungana Y, Chapman NM, Long L, Saravia J, et al. Lipid signalling enforces functional specialization of T(reg) cells in tumours. Nature. 2021;591(7849):306–11.PubMedPubMedCentral Lim SA, Wei J, Nguyen TM, Shi H, Su W, Palacios G, Dhungana Y, Chapman NM, Long L, Saravia J, et al. Lipid signalling enforces functional specialization of T(reg) cells in tumours. Nature. 2021;591(7849):306–11.PubMedPubMedCentral
177.
go back to reference Kim MJ, Kim K, Park HJ, Kim GR, Hong KH, Oh JH, Son J, Park DJ, Kim D, Choi JM, et al. Deletion of PD-1 destabilizes the lineage identity and metabolic fitness of tumor-infiltrating regulatory T cells. Nat Immunol. 2023;24(1):148–61.PubMed Kim MJ, Kim K, Park HJ, Kim GR, Hong KH, Oh JH, Son J, Park DJ, Kim D, Choi JM, et al. Deletion of PD-1 destabilizes the lineage identity and metabolic fitness of tumor-infiltrating regulatory T cells. Nat Immunol. 2023;24(1):148–61.PubMed
178.
go back to reference Pacella I, Procaccini C, Focaccetti C, Miacci S, Timperi E, Faicchia D, Severa M, Rizzo F, Coccia EM, Bonacina F, et al. Fatty acid metabolism complements glycolysis in the selective regulatory T cell expansion during tumor growth. Proc Natl Acad Sci. 2018;115(28):E6546–55.PubMedPubMedCentral Pacella I, Procaccini C, Focaccetti C, Miacci S, Timperi E, Faicchia D, Severa M, Rizzo F, Coccia EM, Bonacina F, et al. Fatty acid metabolism complements glycolysis in the selective regulatory T cell expansion during tumor growth. Proc Natl Acad Sci. 2018;115(28):E6546–55.PubMedPubMedCentral
179.
go back to reference Zeng H, Yang K, Cloer C, Neale G, Vogel P, Chi H. mTORC1 couples immune signals and metabolic programming to establish T(reg)-cell function. Nature. 2013;499(7459):485–90.PubMedPubMedCentral Zeng H, Yang K, Cloer C, Neale G, Vogel P, Chi H. mTORC1 couples immune signals and metabolic programming to establish T(reg)-cell function. Nature. 2013;499(7459):485–90.PubMedPubMedCentral
180.
go back to reference Zhao R, Wan Q, Wang Y, Wu Y, Xiao S, Li Q, Shen X, Zhuang W, Zhou Y, Xia L, et al. M1-like TAMs are required for the efficacy of PD-L1/PD-1 blockades in gastric cancer. Oncoimmunology. 2020;10(1):1862520.PubMedPubMedCentral Zhao R, Wan Q, Wang Y, Wu Y, Xiao S, Li Q, Shen X, Zhuang W, Zhou Y, Xia L, et al. M1-like TAMs are required for the efficacy of PD-L1/PD-1 blockades in gastric cancer. Oncoimmunology. 2020;10(1):1862520.PubMedPubMedCentral
181.
go back to reference Yang M, McKay D, Pollard JW, Lewis CE. Diverse functions of macrophages in different tumor microenvironments. Cancer Res. 2018;78(19):5492–503.PubMedPubMedCentral Yang M, McKay D, Pollard JW, Lewis CE. Diverse functions of macrophages in different tumor microenvironments. Cancer Res. 2018;78(19):5492–503.PubMedPubMedCentral
182.
183.
go back to reference Heusinkveld M, de Vos van Steenwijk PJ, Goedemans R, Ramwadhdoebe TH, Gorter A, Welters MJ, van Hall T, van der Burg SH. M2 macrophages induced by prostaglandin E2 and IL-6 from cervical carcinoma are switched to activated M1 macrophages by CD4+ Th1 cells. J Immunol. 2011;187(3):1157–65.PubMed Heusinkveld M, de Vos van Steenwijk PJ, Goedemans R, Ramwadhdoebe TH, Gorter A, Welters MJ, van Hall T, van der Burg SH. M2 macrophages induced by prostaglandin E2 and IL-6 from cervical carcinoma are switched to activated M1 macrophages by CD4+ Th1 cells. J Immunol. 2011;187(3):1157–65.PubMed
184.
go back to reference Feng Y, Xiao M, Zhang Z, Cui R, Jiang X, Wang S, Bai H, Liu C, Zhang Z. Potential interaction between lysophosphatidic acid and tumor-associated macrophages in ovarian carcinoma. J Inflamm (Lond). 2020;17:23.PubMed Feng Y, Xiao M, Zhang Z, Cui R, Jiang X, Wang S, Bai H, Liu C, Zhang Z. Potential interaction between lysophosphatidic acid and tumor-associated macrophages in ovarian carcinoma. J Inflamm (Lond). 2020;17:23.PubMed
185.
go back to reference Linton SS, Abraham T, Liao J, Clawson GA, Butler PJ, Fox T, Kester M, Matters GL. Tumor-promoting effects of pancreatic cancer cell exosomes on THP-1-derived macrophages. PLoS ONE. 2018;13(11): e0206759.PubMedPubMedCentral Linton SS, Abraham T, Liao J, Clawson GA, Butler PJ, Fox T, Kester M, Matters GL. Tumor-promoting effects of pancreatic cancer cell exosomes on THP-1-derived macrophages. PLoS ONE. 2018;13(11): e0206759.PubMedPubMedCentral
186.
go back to reference Flaherty SE 3rd, Grijalva A, Xu X, Ables E, Nomani A, Ferrante AW Jr. A lipase-independent pathway of lipid release and immune modulation by adipocytes. Science. 2019;363(6430):989–93.PubMedPubMedCentral Flaherty SE 3rd, Grijalva A, Xu X, Ables E, Nomani A, Ferrante AW Jr. A lipase-independent pathway of lipid release and immune modulation by adipocytes. Science. 2019;363(6430):989–93.PubMedPubMedCentral
187.
go back to reference Su P, Wang Q, Bi E, Ma X, Liu L, Yang M, Qian J, Yi Q. Enhanced lipid accumulation and metabolism are required for the differentiation and activation of tumor-associated macrophages. Cancer Res. 2020;80(7):1438–50.PubMedPubMedCentral Su P, Wang Q, Bi E, Ma X, Liu L, Yang M, Qian J, Yi Q. Enhanced lipid accumulation and metabolism are required for the differentiation and activation of tumor-associated macrophages. Cancer Res. 2020;80(7):1438–50.PubMedPubMedCentral
188.
go back to reference Liu S, Zhang H, Li Y, Zhang Y, Bian Y, Zeng Y, Yao X, Wan J, Chen X, Li J, et al. S100A4 enhances protumor macrophage polarization by control of PPAR-gamma-dependent induction of fatty acid oxidation. J Immunother Cancer. 2021;9(6):e002548.PubMedPubMedCentral Liu S, Zhang H, Li Y, Zhang Y, Bian Y, Zeng Y, Yao X, Wan J, Chen X, Li J, et al. S100A4 enhances protumor macrophage polarization by control of PPAR-gamma-dependent induction of fatty acid oxidation. J Immunother Cancer. 2021;9(6):e002548.PubMedPubMedCentral
189.
go back to reference Yang P, Qin H, Li Y, Xiao A, Zheng E, Zeng H, Su C, Luo X, Lu Q, Liao M, et al. CD36-mediated metabolic crosstalk between tumor cells and macrophages affects liver metastasis. Nat Commun. 2022;13(1):5782.PubMedPubMedCentral Yang P, Qin H, Li Y, Xiao A, Zheng E, Zeng H, Su C, Luo X, Lu Q, Liao M, et al. CD36-mediated metabolic crosstalk between tumor cells and macrophages affects liver metastasis. Nat Commun. 2022;13(1):5782.PubMedPubMedCentral
190.
go back to reference Xu ZZ, Xu S, Kuhlmann A, Kaech SM. The role of CD36 in macrophage lipid metabolism and function in tumor microenvironment. J Immunol. 2020;204(1):240.249. Xu ZZ, Xu S, Kuhlmann A, Kaech SM. The role of CD36 in macrophage lipid metabolism and function in tumor microenvironment. J Immunol. 2020;204(1):240.249.
191.
go back to reference Rabold K, Aschenbrenner A, Thiele C, Boahen CK, Schiltmans A, Smit JWA, Schultze JL, Netea MG, Adema GJ, Netea-Maier RT. Enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics. J Immunother Cancer. 2020;8(2):e000638.PubMedPubMedCentral Rabold K, Aschenbrenner A, Thiele C, Boahen CK, Schiltmans A, Smit JWA, Schultze JL, Netea MG, Adema GJ, Netea-Maier RT. Enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics. J Immunother Cancer. 2020;8(2):e000638.PubMedPubMedCentral
192.
go back to reference Liu C, Chikina M, Deshpande R, Menk AV, Wang T, Tabib T, Brunazzi EA, Vignali KM, Sun M, Stolz DB, et al. Treg cells promote the SREBP1-dependent metabolic fitness of tumor-promoting macrophages via repression of CD8(+) T cell-derived interferon-gamma. Immunity. 2019;51(2):381-397 e386.PubMedPubMedCentral Liu C, Chikina M, Deshpande R, Menk AV, Wang T, Tabib T, Brunazzi EA, Vignali KM, Sun M, Stolz DB, et al. Treg cells promote the SREBP1-dependent metabolic fitness of tumor-promoting macrophages via repression of CD8(+) T cell-derived interferon-gamma. Immunity. 2019;51(2):381-397 e386.PubMedPubMedCentral
193.
go back to reference Bose D, Banerjee S, Chatterjee N, Das S, Saha M, Saha KD. Inhibition of TGF-beta induced lipid droplets switches M2 macrophages to M1 phenotype. Toxicol In Vitro. 2019;58:207–14.PubMed Bose D, Banerjee S, Chatterjee N, Das S, Saha M, Saha KD. Inhibition of TGF-beta induced lipid droplets switches M2 macrophages to M1 phenotype. Toxicol In Vitro. 2019;58:207–14.PubMed
194.
go back to reference Wu H, Han Y, Rodriguez Sillke Y, Deng H, Siddiqui S, Treese C, Schmidt F, Friedrich M, Keye J, Wan J, et al. Lipid droplet-dependent fatty acid metabolism controls the immune suppressive phenotype of tumor-associated macrophages. EMBO Mol Med. 2019;11(11): e10698.PubMedPubMedCentral Wu H, Han Y, Rodriguez Sillke Y, Deng H, Siddiqui S, Treese C, Schmidt F, Friedrich M, Keye J, Wan J, et al. Lipid droplet-dependent fatty acid metabolism controls the immune suppressive phenotype of tumor-associated macrophages. EMBO Mol Med. 2019;11(11): e10698.PubMedPubMedCentral
195.
go back to reference Zhang Q, Wang H, Mao C, Sun M, Dominah G, Chen L, Zhuang Z. Fatty acid oxidation contributes to IL-1beta secretion in M2 macrophages and promotes macrophage-mediated tumor cell migration. Mol Immunol. 2018;94:27–35.PubMed Zhang Q, Wang H, Mao C, Sun M, Dominah G, Chen L, Zhuang Z. Fatty acid oxidation contributes to IL-1beta secretion in M2 macrophages and promotes macrophage-mediated tumor cell migration. Mol Immunol. 2018;94:27–35.PubMed
196.
go back to reference Shu Y, Qin M, Song Y, Tang Q, Huang Y, Shen P, Lu Y. M2 polarization of tumor-associated macrophages is dependent on integrin beta3 via peroxisome proliferator-activated receptor-gamma up-regulation in breast cancer. Immunology. 2020;160(4):345–56.PubMedPubMedCentral Shu Y, Qin M, Song Y, Tang Q, Huang Y, Shen P, Lu Y. M2 polarization of tumor-associated macrophages is dependent on integrin beta3 via peroxisome proliferator-activated receptor-gamma up-regulation in breast cancer. Immunology. 2020;160(4):345–56.PubMedPubMedCentral
197.
go back to reference Gordon SR, Maute RL, Dulken BW, Hutter G, George BM, McCracken MN, Gupta R, Tsai JM, Sinha R, Corey D, et al. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature. 2017;545(7655):495–9.PubMedPubMedCentral Gordon SR, Maute RL, Dulken BW, Hutter G, George BM, McCracken MN, Gupta R, Tsai JM, Sinha R, Corey D, et al. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature. 2017;545(7655):495–9.PubMedPubMedCentral
198.
go back to reference Giovanelli P, Sandoval TA, Cubillos-Ruiz JR. Dendritic cell metabolism and function in tumors. Trends Immunol. 2019;40(8):699–718.PubMed Giovanelli P, Sandoval TA, Cubillos-Ruiz JR. Dendritic cell metabolism and function in tumors. Trends Immunol. 2019;40(8):699–718.PubMed
199.
go back to reference Herber DL, Cao W, Nefedova Y, Novitskiy SV, Nagaraj S, Tyurin VA, Corzo A, Cho HI, Celis E, Lennox B, et al. Lipid accumulation and dendritic cell dysfunction in cancer. Nat Med. 2010;16(8):880–6.PubMedPubMedCentral Herber DL, Cao W, Nefedova Y, Novitskiy SV, Nagaraj S, Tyurin VA, Corzo A, Cho HI, Celis E, Lennox B, et al. Lipid accumulation and dendritic cell dysfunction in cancer. Nat Med. 2010;16(8):880–6.PubMedPubMedCentral
200.
go back to reference O’Neill LA, Pearce EJ. Immunometabolism governs dendritic cell and macrophage function. J Exp Med. 2016;213(1):15–23.PubMedPubMedCentral O’Neill LA, Pearce EJ. Immunometabolism governs dendritic cell and macrophage function. J Exp Med. 2016;213(1):15–23.PubMedPubMedCentral
201.
go back to reference Oh DS, Lee HK. Autophagy protein ATG5 regulates CD36 expression and anti-tumor MHC class II antigen presentation in dendritic cells. Autophagy. 2019;15(12):2091–106.PubMedPubMedCentral Oh DS, Lee HK. Autophagy protein ATG5 regulates CD36 expression and anti-tumor MHC class II antigen presentation in dendritic cells. Autophagy. 2019;15(12):2091–106.PubMedPubMedCentral
202.
go back to reference Cubillos-Ruiz JR, Silberman PC, Rutkowski MR, Chopra S, Perales-Puchalt A, Song M, Zhang S, Bettigole SE, Gupta D, Holcomb K, et al. ER stress sensor XBP1 controls anti-tumor immunity by disrupting dendritic cell homeostasis. Cell. 2015;161(7):1527–38.PubMedPubMedCentral Cubillos-Ruiz JR, Silberman PC, Rutkowski MR, Chopra S, Perales-Puchalt A, Song M, Zhang S, Bettigole SE, Gupta D, Holcomb K, et al. ER stress sensor XBP1 controls anti-tumor immunity by disrupting dendritic cell homeostasis. Cell. 2015;161(7):1527–38.PubMedPubMedCentral
203.
go back to reference Zhao F, Xiao C, Evans KS, Theivanthiran T, DeVito N, Holtzhausen A, Liu J, Liu X, Boczkowski D, Nair S, et al. Paracrine Wnt5a-beta-catenin signaling triggers a metabolic program that drives dendritic cell tolerization. Immunity. 2018;48(1):147–60.PubMedPubMedCentral Zhao F, Xiao C, Evans KS, Theivanthiran T, DeVito N, Holtzhausen A, Liu J, Liu X, Boczkowski D, Nair S, et al. Paracrine Wnt5a-beta-catenin signaling triggers a metabolic program that drives dendritic cell tolerization. Immunity. 2018;48(1):147–60.PubMedPubMedCentral
204.
go back to reference Mace EM, Dongre P, Hsu HT, Sinha P, James AM, Mann SS, Forbes LR, Watkin LB, Orange JS. Cell biological steps and checkpoints in accessing NK cell cytotoxicity. Immunol Cell Biol. 2014;92(3):245–55.PubMedPubMedCentral Mace EM, Dongre P, Hsu HT, Sinha P, James AM, Mann SS, Forbes LR, Watkin LB, Orange JS. Cell biological steps and checkpoints in accessing NK cell cytotoxicity. Immunol Cell Biol. 2014;92(3):245–55.PubMedPubMedCentral
205.
go back to reference Brand A, Singer K, Koehl GE, Kolitzus M, Schoenhammer G, Thiel A, Matos C, Bruss C, Klobuch S, Peter K, et al. LDHA-associated lactic acid production blunts tumor immunosurveillance by t and nk cells. Cell Metab. 2016;24(5):657–71.PubMed Brand A, Singer K, Koehl GE, Kolitzus M, Schoenhammer G, Thiel A, Matos C, Bruss C, Klobuch S, Peter K, et al. LDHA-associated lactic acid production blunts tumor immunosurveillance by t and nk cells. Cell Metab. 2016;24(5):657–71.PubMed
206.
go back to reference Harmon C, Robinson MW, Hand F, Almuaili D, Mentor K, Houlihan DD, Hoti E, Lynch L, Geoghegan J, O’Farrelly C. Lactate-mediated acidification of tumor microenvironment induces apoptosis of liver-resident nk cells in colorectal liver metastasis. Cancer Immunol Res. 2019;7(2):335–46.PubMed Harmon C, Robinson MW, Hand F, Almuaili D, Mentor K, Houlihan DD, Hoti E, Lynch L, Geoghegan J, O’Farrelly C. Lactate-mediated acidification of tumor microenvironment induces apoptosis of liver-resident nk cells in colorectal liver metastasis. Cancer Immunol Res. 2019;7(2):335–46.PubMed
207.
go back to reference Michelet X, Dyck L, Hogan A, Loftus RM, Duquette D, Wei K, Beyaz S, Tavakkoli A, Foley C, Donnelly R, et al. Metabolic reprogramming of natural killer cells in obesity limits antitumor responses. Nat Immunol. 2018;19(12):1330–40.PubMed Michelet X, Dyck L, Hogan A, Loftus RM, Duquette D, Wei K, Beyaz S, Tavakkoli A, Foley C, Donnelly R, et al. Metabolic reprogramming of natural killer cells in obesity limits antitumor responses. Nat Immunol. 2018;19(12):1330–40.PubMed
208.
go back to reference Gong Z, Li Q, Shi J, Liu ET, Shultz LD, Ren G. Lipid-laden lung mesenchymal cells foster breast cancer metastasis via metabolic reprogramming of tumor cells and natural killer cells. Cell Metab. 2022;34(12):1960-1976 e1969.PubMed Gong Z, Li Q, Shi J, Liu ET, Shultz LD, Ren G. Lipid-laden lung mesenchymal cells foster breast cancer metastasis via metabolic reprogramming of tumor cells and natural killer cells. Cell Metab. 2022;34(12):1960-1976 e1969.PubMed
209.
go back to reference Kobayashi T, Lam PY, Jiang H, Bednarska K, Gloury R, Murigneux V, Tay J, Jacquelot N, Li R, Tuong ZK, et al. Increased lipid metabolism impairs NK cell function and mediates adaptation to the lymphoma environment. Blood. 2020;136(26):3004–17.PubMed Kobayashi T, Lam PY, Jiang H, Bednarska K, Gloury R, Murigneux V, Tay J, Jacquelot N, Li R, Tuong ZK, et al. Increased lipid metabolism impairs NK cell function and mediates adaptation to the lymphoma environment. Blood. 2020;136(26):3004–17.PubMed
210.
go back to reference Qin WH, Yang ZS, Li M, Chen Y, Zhao XF, Qin YY, Song JQ, Wang BB, Yuan B, Cui XL, et al. High serum levels of cholesterol increase antitumor functions of nature killer cells and reduce growth of liver tumors in mice. Gastroenterology. 2020;158(6):1713–27.PubMed Qin WH, Yang ZS, Li M, Chen Y, Zhao XF, Qin YY, Song JQ, Wang BB, Yuan B, Cui XL, et al. High serum levels of cholesterol increase antitumor functions of nature killer cells and reduce growth of liver tumors in mice. Gastroenterology. 2020;158(6):1713–27.PubMed
211.
go back to reference Yan D, Adeshakin AO, Xu M, Afolabi LO, Zhang G, Chen YH, Wan X. Lipid metabolic pathways confer the immunosuppressive function of myeloid-derived suppressor cells in tumor. Front Immunol. 2019;10:1399.PubMedPubMedCentral Yan D, Adeshakin AO, Xu M, Afolabi LO, Zhang G, Chen YH, Wan X. Lipid metabolic pathways confer the immunosuppressive function of myeloid-derived suppressor cells in tumor. Front Immunol. 2019;10:1399.PubMedPubMedCentral
212.
go back to reference Marvel D, Gabrilovich DI. Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected. J Clin Invest. 2015;125(9):3356–64.PubMedPubMedCentral Marvel D, Gabrilovich DI. Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected. J Clin Invest. 2015;125(9):3356–64.PubMedPubMedCentral
213.
go back to reference Xiang X, Poliakov A, Liu C, Liu Y, Deng ZB, Wang J, Cheng Z, Shah SV, Wang GJ, Zhang L, et al. Induction of myeloid-derived suppressor cells by tumor exosomes. Int J Cancer. 2009;124(11):2621–33.PubMedPubMedCentral Xiang X, Poliakov A, Liu C, Liu Y, Deng ZB, Wang J, Cheng Z, Shah SV, Wang GJ, Zhang L, et al. Induction of myeloid-derived suppressor cells by tumor exosomes. Int J Cancer. 2009;124(11):2621–33.PubMedPubMedCentral
214.
go back to reference Yan G, Zhao H, Zhang Q, Zhou Y, Wu L, Lei J, Wang X, Zhang J, Zhang X, Zheng L, et al. A RIPK3-PGE(2) circuit mediates myeloid-derived suppressor cell-potentiated colorectal carcinogenesis. Cancer Res. 2018;78(19):5586–99.PubMed Yan G, Zhao H, Zhang Q, Zhou Y, Wu L, Lei J, Wang X, Zhang J, Zhang X, Zheng L, et al. A RIPK3-PGE(2) circuit mediates myeloid-derived suppressor cell-potentiated colorectal carcinogenesis. Cancer Res. 2018;78(19):5586–99.PubMed
215.
go back to reference Porta C, Consonni FM, Morlacchi S, Sangaletti S, Bleve A, Totaro MG, Larghi P, Rimoldi M, Tripodo C, Strauss L, et al. Tumor-derived prostaglandin E2 promotes p50 NF-kappaB-dependent differentiation of monocytic MDSCs. Cancer Res. 2020;80(13):2874–88.PubMed Porta C, Consonni FM, Morlacchi S, Sangaletti S, Bleve A, Totaro MG, Larghi P, Rimoldi M, Tripodo C, Strauss L, et al. Tumor-derived prostaglandin E2 promotes p50 NF-kappaB-dependent differentiation of monocytic MDSCs. Cancer Res. 2020;80(13):2874–88.PubMed
216.
go back to reference Mao Y, Sarhan D, Steven A, Seliger B, Kiessling R, Lundqvist A. Inhibition of tumor-derived prostaglandin-e2 blocks the induction of myeloid-derived suppressor cells and recovers natural killer cell activity. Clin Cancer Res. 2014;20(15):4096–106.PubMed Mao Y, Sarhan D, Steven A, Seliger B, Kiessling R, Lundqvist A. Inhibition of tumor-derived prostaglandin-e2 blocks the induction of myeloid-derived suppressor cells and recovers natural killer cell activity. Clin Cancer Res. 2014;20(15):4096–106.PubMed
217.
go back to reference Wang Y, Jia A, Bi Y, Wang Y, Liu G. Metabolic regulation of myeloid-derived suppressor cell function in cancer. Cells. 2020;9(4):1011.PubMedPubMedCentral Wang Y, Jia A, Bi Y, Wang Y, Liu G. Metabolic regulation of myeloid-derived suppressor cell function in cancer. Cells. 2020;9(4):1011.PubMedPubMedCentral
218.
go back to reference Al-Khami AA, Zheng L, Del Valle L, Hossain F, Wyczechowska D, Zabaleta J, Sanchez MD, Dean MJ, Rodriguez PC, Ochoa AC. Exogenous lipid uptake induces metabolic and functional reprogramming of tumor-associated myeloid-derived suppressor cells. Oncoimmunology. 2017;6(10): e1344804.PubMedPubMedCentral Al-Khami AA, Zheng L, Del Valle L, Hossain F, Wyczechowska D, Zabaleta J, Sanchez MD, Dean MJ, Rodriguez PC, Ochoa AC. Exogenous lipid uptake induces metabolic and functional reprogramming of tumor-associated myeloid-derived suppressor cells. Oncoimmunology. 2017;6(10): e1344804.PubMedPubMedCentral
219.
go back to reference Wu H, Weidinger C, Schmidt F, Keye J, Friedrich M, Yerinde C, Willimsky G, Qin Z, Siegmund B, Glauben R. Oleate but not stearate induces the regulatory phenotype of myeloid suppressor cells. Sci Rep. 2017;7(1):7498.PubMedPubMedCentral Wu H, Weidinger C, Schmidt F, Keye J, Friedrich M, Yerinde C, Willimsky G, Qin Z, Siegmund B, Glauben R. Oleate but not stearate induces the regulatory phenotype of myeloid suppressor cells. Sci Rep. 2017;7(1):7498.PubMedPubMedCentral
220.
go back to reference Shi X, Pang S, Zhou J, Yan G, Sun J, Tan W. Feedback loop between fatty acid transport protein 2 and receptor interacting protein 3 pathways promotes polymorphonuclear neutrophil myeloid-derived suppressor cells-potentiated suppressive immunity in bladder cancer. Mol Biol Rep. 2022;49(12):11643–52.PubMed Shi X, Pang S, Zhou J, Yan G, Sun J, Tan W. Feedback loop between fatty acid transport protein 2 and receptor interacting protein 3 pathways promotes polymorphonuclear neutrophil myeloid-derived suppressor cells-potentiated suppressive immunity in bladder cancer. Mol Biol Rep. 2022;49(12):11643–52.PubMed
221.
go back to reference Adeshakin AO, Liu W, Adeshakin FO, Afolabi LO, Zhang M, Zhang G, Wang L, Li Z, Lin L, Cao Q, et al. Regulation of ROS in myeloid-derived suppressor cells through targeting fatty acid transport protein 2 enhanced anti-PD-L1 tumor immunotherapy. Cell Immunol. 2021;362: 104286.PubMed Adeshakin AO, Liu W, Adeshakin FO, Afolabi LO, Zhang M, Zhang G, Wang L, Li Z, Lin L, Cao Q, et al. Regulation of ROS in myeloid-derived suppressor cells through targeting fatty acid transport protein 2 enhanced anti-PD-L1 tumor immunotherapy. Cell Immunol. 2021;362: 104286.PubMed
222.
go back to reference Hossain F, Al-Khami AA, Wyczechowska D, Hernandez C, Zheng L, Reiss K, Valle LD, Trillo-Tinoco J, Maj T, Zou W, et al. Inhibition of fatty acid oxidation modulates immunosuppressive functions of myeloid-derived suppressor cells and enhances cancer therapies. Cancer Immunol Res. 2015;3(11):1236–47.PubMedPubMedCentral Hossain F, Al-Khami AA, Wyczechowska D, Hernandez C, Zheng L, Reiss K, Valle LD, Trillo-Tinoco J, Maj T, Zou W, et al. Inhibition of fatty acid oxidation modulates immunosuppressive functions of myeloid-derived suppressor cells and enhances cancer therapies. Cancer Immunol Res. 2015;3(11):1236–47.PubMedPubMedCentral
223.
go back to reference Munir R, Lisec J, Swinnen JV, Zaidi N. Too complex to fail? Targeting fatty acid metabolism for cancer therapy. Prog Lipid Res. 2022;85: 101143.PubMed Munir R, Lisec J, Swinnen JV, Zaidi N. Too complex to fail? Targeting fatty acid metabolism for cancer therapy. Prog Lipid Res. 2022;85: 101143.PubMed
224.
go back to reference Luo X, Cheng C, Tan Z, Li N, Tang M, Yang L, Cao Y. Emerging roles of lipid metabolism in cancer metastasis. Mol Cancer. 2017;16(1):76.PubMedPubMedCentral Luo X, Cheng C, Tan Z, Li N, Tang M, Yang L, Cao Y. Emerging roles of lipid metabolism in cancer metastasis. Mol Cancer. 2017;16(1):76.PubMedPubMedCentral
225.
go back to reference Yi M, Li J, Chen S, Cai J, Ban Y, Peng Q, Zhou Y, Zeng Z, Peng S, Li X, et al. Emerging role of lipid metabolism alterations in Cancer stem cells. J Exp Clin Cancer Res. 2018;37(1):118.PubMedPubMedCentral Yi M, Li J, Chen S, Cai J, Ban Y, Peng Q, Zhou Y, Zeng Z, Peng S, Li X, et al. Emerging role of lipid metabolism alterations in Cancer stem cells. J Exp Clin Cancer Res. 2018;37(1):118.PubMedPubMedCentral
227.
go back to reference Goncalves AC, Richiardone E, Jorge J, Polonia B, Xavier CPR, Salaroglio IC, Riganti C, Vasconcelos MH, Corbet C, Sarmento-Ribeiro AB. Impact of cancer metabolism on therapy resistance–clinical implications. Drug Resist Updat. 2021;59: 100797.PubMed Goncalves AC, Richiardone E, Jorge J, Polonia B, Xavier CPR, Salaroglio IC, Riganti C, Vasconcelos MH, Corbet C, Sarmento-Ribeiro AB. Impact of cancer metabolism on therapy resistance–clinical implications. Drug Resist Updat. 2021;59: 100797.PubMed
228.
go back to reference Pascual G, Avgustinova A, Mejetta S, Martin M, Castellanos A, Attolini CS, Berenguer A, Prats N, Toll A, Hueto JA, et al. Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature. 2017;541(7635):41–5.PubMed Pascual G, Avgustinova A, Mejetta S, Martin M, Castellanos A, Attolini CS, Berenguer A, Prats N, Toll A, Hueto JA, et al. Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature. 2017;541(7635):41–5.PubMed
229.
go back to reference Watt MJ, Clark AK, Selth LA, Haynes VR, Lister N, Rebello R, Porter LH, Niranjan B, Whitby ST, Lo J, et al. Suppressing fatty acid uptake has therapeutic effects in preclinical models of prostate cancer. Sci Transl Med. 2019;11(478):eaau5758.PubMed Watt MJ, Clark AK, Selth LA, Haynes VR, Lister N, Rebello R, Porter LH, Niranjan B, Whitby ST, Lo J, et al. Suppressing fatty acid uptake has therapeutic effects in preclinical models of prostate cancer. Sci Transl Med. 2019;11(478):eaau5758.PubMed
230.
go back to reference Ligorio F, Di Cosimo S, Verderio P, Ciniselli CM, Pizzamiglio S, Castagnoli L, Dugo M, Galbardi B, Salgado R, Loi S, et al. Predictive role of CD36 expression in HER2-positive breast cancer patients receiving neoadjuvant trastuzumab. J Natl Cancer Inst. 2022;114(12):1720–7.PubMed Ligorio F, Di Cosimo S, Verderio P, Ciniselli CM, Pizzamiglio S, Castagnoli L, Dugo M, Galbardi B, Salgado R, Loi S, et al. Predictive role of CD36 expression in HER2-positive breast cancer patients receiving neoadjuvant trastuzumab. J Natl Cancer Inst. 2022;114(12):1720–7.PubMed
231.
go back to reference Feng WW, Wilkins O, Bang S, Ung M, Li J, An J, Del Genio C, Canfield K, DiRenzo J, Wells W, et al. CD36-Mediated metabolic rewiring of breast cancer cells promotes resistance to HER2-targeted therapies. Cell Rep. 2019;29(11):3405-3420 e3405.PubMedPubMedCentral Feng WW, Wilkins O, Bang S, Ung M, Li J, An J, Del Genio C, Canfield K, DiRenzo J, Wells W, et al. CD36-Mediated metabolic rewiring of breast cancer cells promotes resistance to HER2-targeted therapies. Cell Rep. 2019;29(11):3405-3420 e3405.PubMedPubMedCentral
233.
go back to reference Ye H, Adane B, Khan N, Sullivan T, Minhajuddin M, Gasparetto M, Stevens B, Pei S, Balys M, Ashton JM, et al. Leukemic stem cells evade chemotherapy by metabolic adaptation to an adipose tissue niche. Cell Stem Cell. 2016;19(1):23–37.PubMedPubMedCentral Ye H, Adane B, Khan N, Sullivan T, Minhajuddin M, Gasparetto M, Stevens B, Pei S, Balys M, Ashton JM, et al. Leukemic stem cells evade chemotherapy by metabolic adaptation to an adipose tissue niche. Cell Stem Cell. 2016;19(1):23–37.PubMedPubMedCentral
234.
go back to reference Kubo M, Gotoh K, Eguchi H, Kobayashi S, Iwagami Y, Tomimaru Y, Akita H, Asaoka T, Noda T, Takeda Y, et al. Impact of CD36 on chemoresistance in pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2020;27(2):610–9.PubMed Kubo M, Gotoh K, Eguchi H, Kobayashi S, Iwagami Y, Tomimaru Y, Akita H, Asaoka T, Noda T, Takeda Y, et al. Impact of CD36 on chemoresistance in pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2020;27(2):610–9.PubMed
236.
go back to reference Carbonetti G, Converso C, Clement T, Wang C, Trotman LC, Ojima I, Kaczocha M. Docetaxel/cabazitaxel and fatty acid binding protein 5 inhibitors produce synergistic inhibition of prostate cancer growth. Prostate. 2020;80(1):88–98.PubMed Carbonetti G, Converso C, Clement T, Wang C, Trotman LC, Ojima I, Kaczocha M. Docetaxel/cabazitaxel and fatty acid binding protein 5 inhibitors produce synergistic inhibition of prostate cancer growth. Prostate. 2020;80(1):88–98.PubMed
237.
go back to reference Mukherjee A, Chiang CY, Daifotis HA, Nieman KM, Fahrmann JF, Lastra RR, Romero IL, Fiehn O, Lengyel E. Adipocyte-induced FABP4 expression in ovarian cancer cells promotes metastasis and mediates carboplatin resistance. Cancer Res. 2020;80(8):1748–61.PubMedPubMedCentral Mukherjee A, Chiang CY, Daifotis HA, Nieman KM, Fahrmann JF, Lastra RR, Romero IL, Fiehn O, Lengyel E. Adipocyte-induced FABP4 expression in ovarian cancer cells promotes metastasis and mediates carboplatin resistance. Cancer Res. 2020;80(8):1748–61.PubMedPubMedCentral
238.
go back to reference Alicea GM, Rebecca VW, Goldman AR, Fane ME, Douglass SM, Behera R, Webster MR, Kugel CH 3rd, Ecker BL, Caino MC, et al. Changes in aged fibroblast lipid metabolism induce age-dependent melanoma cell resistance to targeted therapy via the fatty acid transporter FATP2. Cancer Discov. 2020;10(9):1282–95.PubMedPubMedCentral Alicea GM, Rebecca VW, Goldman AR, Fane ME, Douglass SM, Behera R, Webster MR, Kugel CH 3rd, Ecker BL, Caino MC, et al. Changes in aged fibroblast lipid metabolism induce age-dependent melanoma cell resistance to targeted therapy via the fatty acid transporter FATP2. Cancer Discov. 2020;10(9):1282–95.PubMedPubMedCentral
239.
go back to reference Guo W, Ma J, Yang Y, Guo S, Zhang W, Zhao T, Yi X, Wang H, Wang S, Liu Y, et al. ATP-citrate lyase epigenetically potentiates oxidative phosphorylation to promote melanoma growth and adaptive resistance to MAPK inhibition. Clin Cancer Res. 2020;26(11):2725–39.PubMed Guo W, Ma J, Yang Y, Guo S, Zhang W, Zhao T, Yi X, Wang H, Wang S, Liu Y, et al. ATP-citrate lyase epigenetically potentiates oxidative phosphorylation to promote melanoma growth and adaptive resistance to MAPK inhibition. Clin Cancer Res. 2020;26(11):2725–39.PubMed
240.
go back to reference Wei X, Shi J, Lin Q, Ma X, Pang Y, Mao H, Li R, Lu W, Wang Y, Liu P. Targeting ACLY attenuates tumor growth and acquired cisplatin resistance in ovarian cancer by inhibiting the PI3K-AKT pathway and activating the AMPK-ROS pathway. Front Oncol. 2021;11: 642229.PubMedPubMedCentral Wei X, Shi J, Lin Q, Ma X, Pang Y, Mao H, Li R, Lu W, Wang Y, Liu P. Targeting ACLY attenuates tumor growth and acquired cisplatin resistance in ovarian cancer by inhibiting the PI3K-AKT pathway and activating the AMPK-ROS pathway. Front Oncol. 2021;11: 642229.PubMedPubMedCentral
241.
go back to reference Luo J, Hong Y, Lu Y, Qiu S, Chaganty BK, Zhang L, Wang X, Li Q, Fan Z. Acetyl-CoA carboxylase rewires cancer metabolism to allow cancer cells to survive inhibition of the Warburg effect by cetuximab. Cancer Lett. 2017;384:39–49.PubMed Luo J, Hong Y, Lu Y, Qiu S, Chaganty BK, Zhang L, Wang X, Li Q, Fan Z. Acetyl-CoA carboxylase rewires cancer metabolism to allow cancer cells to survive inhibition of the Warburg effect by cetuximab. Cancer Lett. 2017;384:39–49.PubMed
242.
go back to reference Svensson RU, Parker SJ, Eichner LJ, Kolar MJ, Wallace M, Brun SN, Lombardo PS, Van Nostrand JL, Hutchins A, Vera L, et al. Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models. Nat Med. 2016;22(10):1108–19.PubMedPubMedCentral Svensson RU, Parker SJ, Eichner LJ, Kolar MJ, Wallace M, Brun SN, Lombardo PS, Van Nostrand JL, Hutchins A, Vera L, et al. Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models. Nat Med. 2016;22(10):1108–19.PubMedPubMedCentral
243.
go back to reference Lally JSV, Ghoshal S, DePeralta DK, Moaven O, Wei L, Masia R, Erstad DJ, Fujiwara N, Leong V, Houde VP, et al. Inhibition of Acetyl-CoA carboxylase by phosphorylation or the inhibitor ND-654 suppresses lipogenesis and hepatocellular carcinoma. Cell Metab. 2019;29(1):174-182 e175.PubMed Lally JSV, Ghoshal S, DePeralta DK, Moaven O, Wei L, Masia R, Erstad DJ, Fujiwara N, Leong V, Houde VP, et al. Inhibition of Acetyl-CoA carboxylase by phosphorylation or the inhibitor ND-654 suppresses lipogenesis and hepatocellular carcinoma. Cell Metab. 2019;29(1):174-182 e175.PubMed
244.
go back to reference Alkhouri N, Lawitz E, Noureddin M, DeFronzo R, Shulman GI. GS-0976 (Firsocostat): an investigational liver-directed acetyl-CoA carboxylase (ACC) inhibitor for the treatment of non-alcoholic steatohepatitis (NASH). Expert Opin Investig Drugs. 2020;29(2):135–41.PubMed Alkhouri N, Lawitz E, Noureddin M, DeFronzo R, Shulman GI. GS-0976 (Firsocostat): an investigational liver-directed acetyl-CoA carboxylase (ACC) inhibitor for the treatment of non-alcoholic steatohepatitis (NASH). Expert Opin Investig Drugs. 2020;29(2):135–41.PubMed
245.
go back to reference Li Y, Yang W, Zheng Y, Dai W, Ji J, Wu L, Cheng Z, Zhang J, Li J, Xu X, et al. Targeting fatty acid synthase modulates sensitivity of hepatocellular carcinoma to sorafenib via ferroptosis. J Exp Clin Cancer Res. 2023;42(1):6.PubMedPubMedCentral Li Y, Yang W, Zheng Y, Dai W, Ji J, Wu L, Cheng Z, Zhang J, Li J, Xu X, et al. Targeting fatty acid synthase modulates sensitivity of hepatocellular carcinoma to sorafenib via ferroptosis. J Exp Clin Cancer Res. 2023;42(1):6.PubMedPubMedCentral
246.
go back to reference Shueng PW, Chan HW, Lin WC, Kuo DY, Chuang HY. Orlistat resensitizes sorafenib-resistance in hepatocellular carcinoma cells through modulating metabolism. Int J Mol Sci. 2022;23(12):6501.PubMedPubMedCentral Shueng PW, Chan HW, Lin WC, Kuo DY, Chuang HY. Orlistat resensitizes sorafenib-resistance in hepatocellular carcinoma cells through modulating metabolism. Int J Mol Sci. 2022;23(12):6501.PubMedPubMedCentral
247.
go back to reference Chuang HY, Lee YP, Lin WC, Lin YH, Hwang JJ. Fatty acid inhibition sensitizes androgen-dependent and -independent prostate cancer to radiotherapy via FASN/NF-kappaB pathway. Sci Rep. 2019;9(1):13284.PubMedPubMedCentral Chuang HY, Lee YP, Lin WC, Lin YH, Hwang JJ. Fatty acid inhibition sensitizes androgen-dependent and -independent prostate cancer to radiotherapy via FASN/NF-kappaB pathway. Sci Rep. 2019;9(1):13284.PubMedPubMedCentral
248.
go back to reference Papaevangelou E, Almeida GS, Box C, deSouza NM, Chung YL. The effect of FASN inhibition on the growth and metabolism of a cisplatin-resistant ovarian carcinoma model. Int J Cancer. 2018;143(4):992–1002.PubMedPubMedCentral Papaevangelou E, Almeida GS, Box C, deSouza NM, Chung YL. The effect of FASN inhibition on the growth and metabolism of a cisplatin-resistant ovarian carcinoma model. Int J Cancer. 2018;143(4):992–1002.PubMedPubMedCentral
249.
go back to reference Tadros S, Shukla SK, King RJ, Gunda V, Vernucci E, Abrego J, Chaika NV, Yu F, Lazenby AJ, Berim L, et al. De novo lipid synthesis facilitates gemcitabine resistance through endoplasmic reticulum stress in pancreatic cancer. Cancer Res. 2017;77(20):5503–17.PubMedPubMedCentral Tadros S, Shukla SK, King RJ, Gunda V, Vernucci E, Abrego J, Chaika NV, Yu F, Lazenby AJ, Berim L, et al. De novo lipid synthesis facilitates gemcitabine resistance through endoplasmic reticulum stress in pancreatic cancer. Cancer Res. 2017;77(20):5503–17.PubMedPubMedCentral
250.
go back to reference Ali A, Levantini E, Teo JT, Goggi J, Clohessy JG, Wu CS, Chen L, Yang H, Krishnan I, Kocher O, et al. Fatty acid synthase mediates EGFR palmitoylation in EGFR mutated non-small cell lung cancer. EMBO Mol Med. 2018;10(3):e8313.PubMedPubMedCentral Ali A, Levantini E, Teo JT, Goggi J, Clohessy JG, Wu CS, Chen L, Yang H, Krishnan I, Kocher O, et al. Fatty acid synthase mediates EGFR palmitoylation in EGFR mutated non-small cell lung cancer. EMBO Mol Med. 2018;10(3):e8313.PubMedPubMedCentral
251.
go back to reference Wang H, Zhou Y, Xu H, Wang X, Zhang Y, Shang R, O’Farrell M, Roessler S, Sticht C, Stahl A, et al. Therapeutic efficacy of FASN inhibition in preclinical models of HCC. Hepatology. 2022;76(4):951–66.PubMed Wang H, Zhou Y, Xu H, Wang X, Zhang Y, Shang R, O’Farrell M, Roessler S, Sticht C, Stahl A, et al. Therapeutic efficacy of FASN inhibition in preclinical models of HCC. Hepatology. 2022;76(4):951–66.PubMed
252.
go back to reference Liu Y, Gao GF, Minna JD, Williams NS, Westover KD. Loss of wild type KRAS in KRAS(MUT) lung adenocarcinoma is associated with cancer mortality and confers sensitivity to FASN inhibitors. Lung Cancer. 2021;153:73–80.PubMed Liu Y, Gao GF, Minna JD, Williams NS, Westover KD. Loss of wild type KRAS in KRAS(MUT) lung adenocarcinoma is associated with cancer mortality and confers sensitivity to FASN inhibitors. Lung Cancer. 2021;153:73–80.PubMed
253.
go back to reference Sun P, Zhang X, Wang RJ, Ma QY, Xu L, Wang Y, Liao HP, Wang HL, Hu LD, Kong X, et al. PI3Kalpha inhibitor CYH33 triggers antitumor immunity in murine breast cancer by activating CD8(+)T cells and promoting fatty acid metabolism. J Immunother Cancer. 2021;9(8):e003093.PubMedPubMedCentral Sun P, Zhang X, Wang RJ, Ma QY, Xu L, Wang Y, Liao HP, Wang HL, Hu LD, Kong X, et al. PI3Kalpha inhibitor CYH33 triggers antitumor immunity in murine breast cancer by activating CD8(+)T cells and promoting fatty acid metabolism. J Immunother Cancer. 2021;9(8):e003093.PubMedPubMedCentral
254.
go back to reference Heuer TS, Ventura R, Mordec K, Lai J, Fridlib M, Buckley D, Kemble G. FASN inhibition and taxane treatment combine to enhance anti-tumor efficacy in diverse xenograft tumor models through disruption of tubulin palmitoylation and microtubule organization and FASN inhibition-mediated effects on oncogenic signaling and gene expression. EBioMedicine. 2017;16:51–62.PubMed Heuer TS, Ventura R, Mordec K, Lai J, Fridlib M, Buckley D, Kemble G. FASN inhibition and taxane treatment combine to enhance anti-tumor efficacy in diverse xenograft tumor models through disruption of tubulin palmitoylation and microtubule organization and FASN inhibition-mediated effects on oncogenic signaling and gene expression. EBioMedicine. 2017;16:51–62.PubMed
255.
go back to reference Alwarawrah Y, Hughes P, Loiselle D, Carlson DA, Darr DB, Jordan JL, Xiong J, Hunter LM, Dubois LG, Thompson JW, et al. Fasnall, a selective fasn inhibitor, shows potent anti-tumor activity in the MMTV-Neu model of HER2(+) breast cancer. Cell Chem Biol. 2016;23(6):678–88.PubMedPubMedCentral Alwarawrah Y, Hughes P, Loiselle D, Carlson DA, Darr DB, Jordan JL, Xiong J, Hunter LM, Dubois LG, Thompson JW, et al. Fasnall, a selective fasn inhibitor, shows potent anti-tumor activity in the MMTV-Neu model of HER2(+) breast cancer. Cell Chem Biol. 2016;23(6):678–88.PubMedPubMedCentral
256.
go back to reference Polonio-Alcala E, Porta R, Ruiz-Martinez S, Vasquez-Dongo C, Relat J, Bosch-Barrera J, Ciurana J, Puig T. AZ12756122, a novel fatty acid synthase inhibitor, decreases resistance features in EGFR-TKI resistant EGFR-mutated NSCLC cell models. Biomed Pharmacother. 2022;156: 113942.PubMed Polonio-Alcala E, Porta R, Ruiz-Martinez S, Vasquez-Dongo C, Relat J, Bosch-Barrera J, Ciurana J, Puig T. AZ12756122, a novel fatty acid synthase inhibitor, decreases resistance features in EGFR-TKI resistant EGFR-mutated NSCLC cell models. Biomed Pharmacother. 2022;156: 113942.PubMed
257.
go back to reference Falchook G, Infante J, Arkenau HT, Patel MR, Dean E, Borazanci E, Brenner A, Cook N, Lopez J, Pant S, et al. First-in-human study of the safety, pharmacokinetics, and pharmacodynamics of first-in-class fatty acid synthase inhibitor TVB-2640 alone and with a taxane in advanced tumors. EClinicalMedicine. 2021;34: 100797.PubMedPubMedCentral Falchook G, Infante J, Arkenau HT, Patel MR, Dean E, Borazanci E, Brenner A, Cook N, Lopez J, Pant S, et al. First-in-human study of the safety, pharmacokinetics, and pharmacodynamics of first-in-class fatty acid synthase inhibitor TVB-2640 alone and with a taxane in advanced tumors. EClinicalMedicine. 2021;34: 100797.PubMedPubMedCentral
259.
go back to reference Tesfay L, Paul BT, Konstorum A, Deng Z, Cox AO, Lee J, Furdui CM, Hegde P, Torti FM, Torti SV. Stearoyl-CoA desaturase 1 protects ovarian cancer cells from ferroptotic cell death. Cancer Res. 2019;79(20):5355–66.PubMedPubMedCentral Tesfay L, Paul BT, Konstorum A, Deng Z, Cox AO, Lee J, Furdui CM, Hegde P, Torti FM, Torti SV. Stearoyl-CoA desaturase 1 protects ovarian cancer cells from ferroptotic cell death. Cancer Res. 2019;79(20):5355–66.PubMedPubMedCentral
260.
go back to reference Pisanu ME, Maugeri-Sacca M, Fattore L, Bruschini S, De Vitis C, Tabbi E, Bellei B, Migliano E, Kovacs D, Camera E, et al. Inhibition of Stearoyl-CoA desaturase 1 reverts BRAF and MEK inhibition-induced selection of cancer stem cells in BRAF-mutated melanoma. J Exp Clin Cancer Res. 2018;37(1):318.PubMedPubMedCentral Pisanu ME, Maugeri-Sacca M, Fattore L, Bruschini S, De Vitis C, Tabbi E, Bellei B, Migliano E, Kovacs D, Camera E, et al. Inhibition of Stearoyl-CoA desaturase 1 reverts BRAF and MEK inhibition-induced selection of cancer stem cells in BRAF-mutated melanoma. J Exp Clin Cancer Res. 2018;37(1):318.PubMedPubMedCentral
261.
go back to reference von Roemeling CA, Marlow LA, Wei JJ, Cooper SJ, Caulfield TR, Wu K, Tan WW, Tun HW, Copland JA. Stearoyl-CoA desaturase 1 is a novel molecular therapeutic target for clear cell renal cell carcinoma. Clin Cancer Res. 2013;19(9):2368–80. von Roemeling CA, Marlow LA, Wei JJ, Cooper SJ, Caulfield TR, Wu K, Tan WW, Tun HW, Copland JA. Stearoyl-CoA desaturase 1 is a novel molecular therapeutic target for clear cell renal cell carcinoma. Clin Cancer Res. 2013;19(9):2368–80.
262.
go back to reference Dai S, Yan Y, Xu Z, Zeng S, Qian L, Huo L, Li X, Sun L, Gong Z. SCD1 confers temozolomide resistance to human glioma cells via the Akt/GSK3beta/beta-catenin signaling axis. Front Pharmacol. 2017;8:960.PubMed Dai S, Yan Y, Xu Z, Zeng S, Qian L, Huo L, Li X, Sun L, Gong Z. SCD1 confers temozolomide resistance to human glioma cells via the Akt/GSK3beta/beta-catenin signaling axis. Front Pharmacol. 2017;8:960.PubMed
263.
go back to reference Ma MKF, Lau EYT, Leung DHW, Lo J, Ho NPY, Cheng LKW, Ma S, Lin CH, Copland JA, Ding J, et al. Stearoyl-CoA desaturase regulates sorafenib resistance via modulation of ER stress-induced differentiation. J Hepatol. 2017;67(5):979–90.PubMed Ma MKF, Lau EYT, Leung DHW, Lo J, Ho NPY, Cheng LKW, Ma S, Lin CH, Copland JA, Ding J, et al. Stearoyl-CoA desaturase regulates sorafenib resistance via modulation of ER stress-induced differentiation. J Hepatol. 2017;67(5):979–90.PubMed
264.
go back to reference Huang Q, Wang Q, Li D, Wei X, Jia Y, Zhang Z, Ai B, Cao X, Guo T, Liao Y. Co-administration of 20(S)-protopanaxatriol (g-PPT) and EGFR-TKI overcomes EGFR-TKI resistance by decreasing SCD1 induced lipid accumulation in non-small cell lung cancer. J Exp Clin Cancer Res. 2019;38(1):129.PubMedPubMedCentral Huang Q, Wang Q, Li D, Wei X, Jia Y, Zhang Z, Ai B, Cao X, Guo T, Liao Y. Co-administration of 20(S)-protopanaxatriol (g-PPT) and EGFR-TKI overcomes EGFR-TKI resistance by decreasing SCD1 induced lipid accumulation in non-small cell lung cancer. J Exp Clin Cancer Res. 2019;38(1):129.PubMedPubMedCentral
265.
go back to reference Pisanu ME, Noto A, De Vitis C, Morrone S, Scognamiglio G, Botti G, Venuta F, Diso D, Jakopin Z, Padula F, et al. Blockade of Stearoyl-CoA-desaturase 1 activity reverts resistance to cisplatin in lung cancer stem cells. Cancer Lett. 2017;406:93–104.PubMed Pisanu ME, Noto A, De Vitis C, Morrone S, Scognamiglio G, Botti G, Venuta F, Diso D, Jakopin Z, Padula F, et al. Blockade of Stearoyl-CoA-desaturase 1 activity reverts resistance to cisplatin in lung cancer stem cells. Cancer Lett. 2017;406:93–104.PubMed
266.
go back to reference Talebi A, Dehairs J, Rambow F, Rogiers A, Nittner D, Derua R, Vanderhoydonc F, Duarte JAG, Bosisio F, Van den Eynde K, et al. Sustained SREBP-1-dependent lipogenesis as a key mediator of resistance to BRAF-targeted therapy. Nat Commun. 2018;9(1):2500.PubMedPubMedCentral Talebi A, Dehairs J, Rambow F, Rogiers A, Nittner D, Derua R, Vanderhoydonc F, Duarte JAG, Bosisio F, Van den Eynde K, et al. Sustained SREBP-1-dependent lipogenesis as a key mediator of resistance to BRAF-targeted therapy. Nat Commun. 2018;9(1):2500.PubMedPubMedCentral
267.
go back to reference Yin F, Feng F, Wang L, Wang X, Li Z, Cao Y. SREBP-1 inhibitor Betulin enhances the antitumor effect of Sorafenib on hepatocellular carcinoma via restricting cellular glycolytic activity. Cell Death Dis. 2019;10(9):672.PubMedPubMedCentral Yin F, Feng F, Wang L, Wang X, Li Z, Cao Y. SREBP-1 inhibitor Betulin enhances the antitumor effect of Sorafenib on hepatocellular carcinoma via restricting cellular glycolytic activity. Cell Death Dis. 2019;10(9):672.PubMedPubMedCentral
268.
go back to reference Dechaphunkul T, Arundon T, Raungkhajon P, Jiratrachu R, Geater SL, Dechaphunkul A. Benefits of immunonutrition in patients with head and neck cancer receiving chemoradiation: a phase II randomized, double-blind study. Clin Nutr. 2022;41(2):433–40.PubMed Dechaphunkul T, Arundon T, Raungkhajon P, Jiratrachu R, Geater SL, Dechaphunkul A. Benefits of immunonutrition in patients with head and neck cancer receiving chemoradiation: a phase II randomized, double-blind study. Clin Nutr. 2022;41(2):433–40.PubMed
269.
go back to reference Mullen PJ, Yu R, Longo J, Archer MC, Penn LZ. The interplay between cell signalling and the mevalonate pathway in cancer. Nat Rev Cancer. 2016;16(11):718–31.PubMed Mullen PJ, Yu R, Longo J, Archer MC, Penn LZ. The interplay between cell signalling and the mevalonate pathway in cancer. Nat Rev Cancer. 2016;16(11):718–31.PubMed
270.
go back to reference Hagiwara N, Watanabe M, Iizuka-Ohashi M, Yokota I, Toriyama S, Sukeno M, Tomosugi M, Sowa Y, Hongo F, Mikami K, et al. Mevalonate pathway blockage enhances the efficacy of mTOR inhibitors with the activation of retinoblastoma protein in renal cell carcinoma. Cancer Lett. 2018;431:182–9.PubMed Hagiwara N, Watanabe M, Iizuka-Ohashi M, Yokota I, Toriyama S, Sukeno M, Tomosugi M, Sowa Y, Hongo F, Mikami K, et al. Mevalonate pathway blockage enhances the efficacy of mTOR inhibitors with the activation of retinoblastoma protein in renal cell carcinoma. Cancer Lett. 2018;431:182–9.PubMed
271.
go back to reference Kim JS, Turbov J, Rosales R, Thaete LG, Rodriguez GC. Combination simvastatin and metformin synergistically inhibits endometrial cancer cell growth. Gynecol Oncol. 2019;154(2):432–40.PubMed Kim JS, Turbov J, Rosales R, Thaete LG, Rodriguez GC. Combination simvastatin and metformin synergistically inhibits endometrial cancer cell growth. Gynecol Oncol. 2019;154(2):432–40.PubMed
272.
go back to reference Shojaei S, Koleini N, Samiei E, Aghaei M, Cole LK, Alizadeh J, Islam MI, Vosoughi AR, Albokashy M, Butterfield Y, et al. Simvastatin increases temozolomide-induced cell death by targeting the fusion of autophagosomes and lysosomes. FEBS J. 2020;287(5):1005–34.PubMed Shojaei S, Koleini N, Samiei E, Aghaei M, Cole LK, Alizadeh J, Islam MI, Vosoughi AR, Albokashy M, Butterfield Y, et al. Simvastatin increases temozolomide-induced cell death by targeting the fusion of autophagosomes and lysosomes. FEBS J. 2020;287(5):1005–34.PubMed
273.
go back to reference Zhang Y, Liu Y, Duan J, Wang H, Zhang Y, Qiao K, Wang J. Cholesterol depletion sensitizes gallbladder cancer to cisplatin by impairing DNA damage response. Cell Cycle. 2019;18(23):3337–50.PubMedPubMedCentral Zhang Y, Liu Y, Duan J, Wang H, Zhang Y, Qiao K, Wang J. Cholesterol depletion sensitizes gallbladder cancer to cisplatin by impairing DNA damage response. Cell Cycle. 2019;18(23):3337–50.PubMedPubMedCentral
274.
go back to reference Peng Y, He G, Tang D, Xiong L, Wen Y, Miao X, Hong Z, Yao H, Chen C, Yan S, et al. Lovastatin inhibits cancer stem cells and sensitizes to chemo-and photodynamic therapy in nasopharyngeal carcinoma. J Cancer. 2017;8(9):1655–64.PubMedPubMedCentral Peng Y, He G, Tang D, Xiong L, Wen Y, Miao X, Hong Z, Yao H, Chen C, Yan S, et al. Lovastatin inhibits cancer stem cells and sensitizes to chemo-and photodynamic therapy in nasopharyngeal carcinoma. J Cancer. 2017;8(9):1655–64.PubMedPubMedCentral
275.
go back to reference Han JY, Lee SH, Yoo NJ, Hyung LS, Moon YJ, Yun T, Kim HT, Lee JS. A randomized phase II study of gefitinib plus simvastatin versus gefitinib alone in previously treated patients with advanced non-small cell lung cancer. Clin Cancer Res. 2011;17(6):1553–60.PubMed Han JY, Lee SH, Yoo NJ, Hyung LS, Moon YJ, Yun T, Kim HT, Lee JS. A randomized phase II study of gefitinib plus simvastatin versus gefitinib alone in previously treated patients with advanced non-small cell lung cancer. Clin Cancer Res. 2011;17(6):1553–60.PubMed
276.
go back to reference Yulian ED, Siregar NC, Bajuadji. Combination of simvastatin and FAC improves response to neoadjuvant chemotherapy in locally advanced breast cancer. Cancer Res Treat. 2021;53(4):1072–83.PubMedPubMedCentral Yulian ED, Siregar NC, Bajuadji. Combination of simvastatin and FAC improves response to neoadjuvant chemotherapy in locally advanced breast cancer. Cancer Res Treat. 2021;53(4):1072–83.PubMedPubMedCentral
277.
go back to reference Kim ST, Kang JH, Lee J, Park SH, Park JO, Park YS, Lim HY, Hwang IG, Lee SC, Park KW, et al. Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer. 2014;50(16):2822–30.PubMed Kim ST, Kang JH, Lee J, Park SH, Park JO, Park YS, Lim HY, Hwang IG, Lee SC, Park KW, et al. Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer. 2014;50(16):2822–30.PubMed
278.
go back to reference Siltari A, Riikonen J, Koskimaki J, Pakarainen T, Ettala O, Bostrom P, Seikkula H, Kotsar A, Tammela T, Helminen M, et al. Randomised double-blind phase 3 clinical study testing impact of atorvastatin on prostate cancer progression after initiation of androgen deprivation therapy: study protocol. BMJ Open. 2022;12(4): e050264.PubMedPubMedCentral Siltari A, Riikonen J, Koskimaki J, Pakarainen T, Ettala O, Bostrom P, Seikkula H, Kotsar A, Tammela T, Helminen M, et al. Randomised double-blind phase 3 clinical study testing impact of atorvastatin on prostate cancer progression after initiation of androgen deprivation therapy: study protocol. BMJ Open. 2022;12(4): e050264.PubMedPubMedCentral
279.
go back to reference de la Cueva A, Ramirez de Molina A, Alvarez-Ayerza N, Ramos MA, Cebrian A, Del Pulgar TG, Lacal JC. Combined 5-FU and ChoKalpha inhibitors as a new alternative therapy of colorectal cancer: evidence in human tumor-derived cell lines and mouse xenografts. PLoS ONE. 2013;8(6):e64961.PubMedPubMedCentral de la Cueva A, Ramirez de Molina A, Alvarez-Ayerza N, Ramos MA, Cebrian A, Del Pulgar TG, Lacal JC. Combined 5-FU and ChoKalpha inhibitors as a new alternative therapy of colorectal cancer: evidence in human tumor-derived cell lines and mouse xenografts. PLoS ONE. 2013;8(6):e64961.PubMedPubMedCentral
280.
go back to reference Mazarico JM, Sanchez-Arevalo Lobo VJ, Favicchio R, Greenhalf W, Costello E, Carrillo-de Santa Pau E, Marques M, Lacal JC, Aboagye E, Real FX. Choline kinase alpha (CHKalpha) as a therapeutic target in pancreatic ductal adenocarcinoma: expression, predictive value, and sensitivity to inhibitors. Mol Cancer Ther. 2016;15(2):323–33.PubMed Mazarico JM, Sanchez-Arevalo Lobo VJ, Favicchio R, Greenhalf W, Costello E, Carrillo-de Santa Pau E, Marques M, Lacal JC, Aboagye E, Real FX. Choline kinase alpha (CHKalpha) as a therapeutic target in pancreatic ductal adenocarcinoma: expression, predictive value, and sensitivity to inhibitors. Mol Cancer Ther. 2016;15(2):323–33.PubMed
281.
go back to reference Abalsamo L, Spadaro F, Bozzuto G, Paris L, Cecchetti S, Lugini L, Iorio E, Molinari A, Ramoni C, Podo F. Inhibition of phosphatidylcholine-specific phospholipase C results in loss of mesenchymal traits in metastatic breast cancer cells. Breast Cancer Res. 2012;14(2):R50.PubMedPubMedCentral Abalsamo L, Spadaro F, Bozzuto G, Paris L, Cecchetti S, Lugini L, Iorio E, Molinari A, Ramoni C, Podo F. Inhibition of phosphatidylcholine-specific phospholipase C results in loss of mesenchymal traits in metastatic breast cancer cells. Breast Cancer Res. 2012;14(2):R50.PubMedPubMedCentral
282.
go back to reference Chen Q, Hongu T, Sato T, Zhang Y, Ali W, Cavallo JA, van der Velden A, Tian H, Di Paolo G, Nieswandt B, et al. Key roles for the lipid signaling enzyme phospholipase d1 in the tumor microenvironment during tumor angiogenesis and metastasis. Sci Signal. 2012;5(249):ra79.PubMedPubMedCentral Chen Q, Hongu T, Sato T, Zhang Y, Ali W, Cavallo JA, van der Velden A, Tian H, Di Paolo G, Nieswandt B, et al. Key roles for the lipid signaling enzyme phospholipase d1 in the tumor microenvironment during tumor angiogenesis and metastasis. Sci Signal. 2012;5(249):ra79.PubMedPubMedCentral
283.
go back to reference Wang D, Cabalag CS, Clemons NJ, DuBois RN. Cyclooxygenases and prostaglandins in tumor immunology and microenvironment of gastrointestinal cancer. Gastroenterology. 2021;161(6):1813–29.PubMed Wang D, Cabalag CS, Clemons NJ, DuBois RN. Cyclooxygenases and prostaglandins in tumor immunology and microenvironment of gastrointestinal cancer. Gastroenterology. 2021;161(6):1813–29.PubMed
284.
go back to reference Samudio I, Harmancey R, Fiegl M, Kantarjian H, Konopleva M, Korchin B, Kaluarachchi K, Bornmann W, Duvvuri S, Taegtmeyer H, et al. Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. J Clin Invest. 2010;120(1):142–56.PubMed Samudio I, Harmancey R, Fiegl M, Kantarjian H, Konopleva M, Korchin B, Kaluarachchi K, Bornmann W, Duvvuri S, Taegtmeyer H, et al. Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. J Clin Invest. 2010;120(1):142–56.PubMed
285.
go back to reference Yu S, Li Q, Yu Y, Cui Y, Li W, Liu T, Liu F. Activated HIF1alpha of tumor cells promotes chemoresistance development via recruiting GDF15-producing tumor-associated macrophages in gastric cancer. Cancer Immunol Immunother. 2020;69(10):1973–87.PubMed Yu S, Li Q, Yu Y, Cui Y, Li W, Liu T, Liu F. Activated HIF1alpha of tumor cells promotes chemoresistance development via recruiting GDF15-producing tumor-associated macrophages in gastric cancer. Cancer Immunol Immunother. 2020;69(10):1973–87.PubMed
286.
go back to reference Tan Z, Xiao L, Tang M, Bai F, Li J, Li L, Shi F, Li N, Li Y, Du Q, et al. Targeting CPT1A-mediated fatty acid oxidation sensitizes nasopharyngeal carcinoma to radiation therapy. Theranostics. 2018;8(9):2329–47.PubMedPubMedCentral Tan Z, Xiao L, Tang M, Bai F, Li J, Li L, Shi F, Li N, Li Y, Du Q, et al. Targeting CPT1A-mediated fatty acid oxidation sensitizes nasopharyngeal carcinoma to radiation therapy. Theranostics. 2018;8(9):2329–47.PubMedPubMedCentral
287.
go back to reference Iwamoto H, Abe M, Yang Y, Cui D, Seki T, Nakamura M, Hosaka K, Lim S, Wu J, He X, et al. Cancer lipid metabolism confers antiangiogenic drug resistance. Cell Metab. 2018;28(1):104-117 e105.PubMed Iwamoto H, Abe M, Yang Y, Cui D, Seki T, Nakamura M, Hosaka K, Lim S, Wu J, He X, et al. Cancer lipid metabolism confers antiangiogenic drug resistance. Cell Metab. 2018;28(1):104-117 e105.PubMed
288.
go back to reference Holubarsch CJ, Rohrbach M, Karrasch M, Boehm E, Polonski L, Ponikowski P, Rhein S. A double-blind randomized multicentre clinical trial to evaluate the efficacy and safety of two doses of etomoxir in comparison with placebo in patients with moderate congestive heart failure: the ERGO (etomoxir for the recovery of glucose oxidation) study. Clin Sci (Lond). 2007;113(4):205–12.PubMed Holubarsch CJ, Rohrbach M, Karrasch M, Boehm E, Polonski L, Ponikowski P, Rhein S. A double-blind randomized multicentre clinical trial to evaluate the efficacy and safety of two doses of etomoxir in comparison with placebo in patients with moderate congestive heart failure: the ERGO (etomoxir for the recovery of glucose oxidation) study. Clin Sci (Lond). 2007;113(4):205–12.PubMed
289.
go back to reference Reyes-Castellanos G, Abdel Hadi N, Gallardo-Arriaga S, Masoud R, Garcia J, Lac S, El Kaoutari A, Gicquel T, Planque M, Fendt SM, et al. Combining the antianginal drug perhexiline with chemotherapy induces complete pancreatic cancer regression in vivo. Iscience. 2023;26(6):106899.PubMedPubMedCentral Reyes-Castellanos G, Abdel Hadi N, Gallardo-Arriaga S, Masoud R, Garcia J, Lac S, El Kaoutari A, Gicquel T, Planque M, Fendt SM, et al. Combining the antianginal drug perhexiline with chemotherapy induces complete pancreatic cancer regression in vivo. Iscience. 2023;26(6):106899.PubMedPubMedCentral
290.
go back to reference Zhu J, Wu G, Song L, Cao L, Tan Z, Tang M, Li Z, Shi D, Zhang S, Li J. NKX2-8 deletion-induced reprogramming of fatty acid metabolism confers chemoresistance in epithelial ovarian cancer. EBioMedicine. 2019;43:238–52.PubMedPubMedCentral Zhu J, Wu G, Song L, Cao L, Tan Z, Tang M, Li Z, Shi D, Zhang S, Li J. NKX2-8 deletion-induced reprogramming of fatty acid metabolism confers chemoresistance in epithelial ovarian cancer. EBioMedicine. 2019;43:238–52.PubMedPubMedCentral
291.
go back to reference Wang T, Fahrmann JF, Lee H, Li YJ, Tripathi SC, Yue C, Zhang C, Lifshitz V, Song J, Yuan Y, et al. JAK/STAT3-regulated fatty acid beta-oxidation is critical for breast cancer stem cell self-renewal and chemoresistance. Cell Metab. 2018;27(1):136-150 e135.PubMed Wang T, Fahrmann JF, Lee H, Li YJ, Tripathi SC, Yue C, Zhang C, Lifshitz V, Song J, Yuan Y, et al. JAK/STAT3-regulated fatty acid beta-oxidation is critical for breast cancer stem cell self-renewal and chemoresistance. Cell Metab. 2018;27(1):136-150 e135.PubMed
292.
go back to reference Ricciardi MR, Mirabilii S, Allegretti M, Licchetta R, Calarco A, Torrisi MR, Foa R, Nicolai R, Peluso G, Tafuri A. Targeting the leukemia cell metabolism by the CPT1a inhibition: functional preclinical effects in leukemias. Blood. 2015;126(16):1925–9.PubMed Ricciardi MR, Mirabilii S, Allegretti M, Licchetta R, Calarco A, Torrisi MR, Foa R, Nicolai R, Peluso G, Tafuri A. Targeting the leukemia cell metabolism by the CPT1a inhibition: functional preclinical effects in leukemias. Blood. 2015;126(16):1925–9.PubMed
293.
go back to reference Wu C, Dai C, Li X, Sun M, Chu H, Xuan Q, Yin Y, Fang C, Yang F, Jiang Z, et al. AKR1C3-dependent lipid droplet formation confers hepatocellular carcinoma cell adaptability to targeted therapy. Theranostics. 2022;12(18):7681–98.PubMedPubMedCentral Wu C, Dai C, Li X, Sun M, Chu H, Xuan Q, Yin Y, Fang C, Yang F, Jiang Z, et al. AKR1C3-dependent lipid droplet formation confers hepatocellular carcinoma cell adaptability to targeted therapy. Theranostics. 2022;12(18):7681–98.PubMedPubMedCentral
294.
go back to reference Chen L, Ma WL, Cheng WC, Yang JC, Wang HC, Su YT, Ahmad A, Hung YC, Chang WC. Targeting lipid droplet lysophosphatidylcholine for cisplatin chemotherapy. J Cell Mol Med. 2020;24(13):7187–200.PubMedPubMedCentral Chen L, Ma WL, Cheng WC, Yang JC, Wang HC, Su YT, Ahmad A, Hung YC, Chang WC. Targeting lipid droplet lysophosphatidylcholine for cisplatin chemotherapy. J Cell Mol Med. 2020;24(13):7187–200.PubMedPubMedCentral
295.
go back to reference Cotte AK, Aires V, Fredon M, Limagne E, Derangere V, Thibaudin M, Humblin E, Scagliarini A, de Barros JP, Hillon P, et al. Lysophosphatidylcholine acyltransferase 2-mediated lipid droplet production supports colorectal cancer chemoresistance. Nat Commun. 2018;9(1):322.PubMedPubMedCentral Cotte AK, Aires V, Fredon M, Limagne E, Derangere V, Thibaudin M, Humblin E, Scagliarini A, de Barros JP, Hillon P, et al. Lysophosphatidylcholine acyltransferase 2-mediated lipid droplet production supports colorectal cancer chemoresistance. Nat Commun. 2018;9(1):322.PubMedPubMedCentral
296.
go back to reference Tirinato L, Pagliari F, Di Franco S, Sogne E, Marafioti MG, Jansen J, Falqui A, Todaro M, Candeloro P, Liberale C, et al. ROS and Lipid Droplet accumulation induced by high glucose exposure in healthy colon and Colorectal Cancer Stem Cells. Genes Dis. 2020;7(4):620–35.PubMed Tirinato L, Pagliari F, Di Franco S, Sogne E, Marafioti MG, Jansen J, Falqui A, Todaro M, Candeloro P, Liberale C, et al. ROS and Lipid Droplet accumulation induced by high glucose exposure in healthy colon and Colorectal Cancer Stem Cells. Genes Dis. 2020;7(4):620–35.PubMed
297.
go back to reference Senkal CE, Salama MF, Snider AJ, Allopenna JJ, Rana NA, Koller A, Hannun YA, Obeid LM. Ceramide is metabolized to acylceramide and stored in lipid droplets. Cell Metab. 2017;25(3):686–97.PubMedPubMedCentral Senkal CE, Salama MF, Snider AJ, Allopenna JJ, Rana NA, Koller A, Hannun YA, Obeid LM. Ceramide is metabolized to acylceramide and stored in lipid droplets. Cell Metab. 2017;25(3):686–97.PubMedPubMedCentral
298.
go back to reference Hernandez-Corbacho MJ, Obeid LM. A novel role for DGATs in cancer. Adv Biol Regul. 2019;72:89–101.PubMed Hernandez-Corbacho MJ, Obeid LM. A novel role for DGATs in cancer. Adv Biol Regul. 2019;72:89–101.PubMed
299.
go back to reference Nistico C, Pagliari F, Chiarella E, Fernandes Guerreiro J, Marafioti MG, Aversa I, Genard G, Hanley R, Garcia-Calderon D, Bond HM, et al. Lipid droplet biosynthesis impairment through DGAT2 inhibition sensitizes MCF7 breast cancer cells to radiation. Int J Mol Sci. 2021;22(18):10102.PubMedPubMedCentral Nistico C, Pagliari F, Chiarella E, Fernandes Guerreiro J, Marafioti MG, Aversa I, Genard G, Hanley R, Garcia-Calderon D, Bond HM, et al. Lipid droplet biosynthesis impairment through DGAT2 inhibition sensitizes MCF7 breast cancer cells to radiation. Int J Mol Sci. 2021;22(18):10102.PubMedPubMedCentral
300.
go back to reference Li J, Gu D, Lee SS, Song B, Bandyopadhyay S, Chen S, Konieczny SF, Ratliff TL, Liu X, Xie J, et al. Abrogating cholesterol esterification suppresses growth and metastasis of pancreatic cancer. Oncogene. 2016;35(50):6378–88.PubMedPubMedCentral Li J, Gu D, Lee SS, Song B, Bandyopadhyay S, Chen S, Konieczny SF, Ratliff TL, Liu X, Xie J, et al. Abrogating cholesterol esterification suppresses growth and metastasis of pancreatic cancer. Oncogene. 2016;35(50):6378–88.PubMedPubMedCentral
301.
go back to reference Jiang Y, Sun A, Zhao Y, Ying W, Sun H, Yang X, Xing B, Sun W, Ren L, Hu B, et al. Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma. Nature. 2019;567(7747):257–61.PubMed Jiang Y, Sun A, Zhao Y, Ying W, Sun H, Yang X, Xing B, Sun W, Ren L, Hu B, et al. Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma. Nature. 2019;567(7747):257–61.PubMed
302.
go back to reference Lee SS, Li J, Tai JN, Ratliff TL, Park K, Cheng JX. Avasimibe encapsulated in human serum albumin blocks cholesterol esterification for selective cancer treatment. ACS Nano. 2015;9(3):2420–32.PubMedPubMedCentral Lee SS, Li J, Tai JN, Ratliff TL, Park K, Cheng JX. Avasimibe encapsulated in human serum albumin blocks cholesterol esterification for selective cancer treatment. ACS Nano. 2015;9(3):2420–32.PubMedPubMedCentral
303.
go back to reference Li M, Yang Y, Wei J, Cun X, Lu Z, Qiu Y, Zhang Z, He Q. Enhanced chemo-immunotherapy against melanoma by inhibition of cholesterol esterification in CD8(+) T cells. Nanomedicine. 2018;14(8):2541–50.PubMed Li M, Yang Y, Wei J, Cun X, Lu Z, Qiu Y, Zhang Z, He Q. Enhanced chemo-immunotherapy against melanoma by inhibition of cholesterol esterification in CD8(+) T cells. Nanomedicine. 2018;14(8):2541–50.PubMed
304.
go back to reference Li J, Qu X, Tian J, Zhang JT, Cheng JX. Cholesterol esterification inhibition and gemcitabine synergistically suppress pancreatic ductal adenocarcinoma proliferation. PLoS ONE. 2018;13(2): e0193318.PubMedPubMedCentral Li J, Qu X, Tian J, Zhang JT, Cheng JX. Cholesterol esterification inhibition and gemcitabine synergistically suppress pancreatic ductal adenocarcinoma proliferation. PLoS ONE. 2018;13(2): e0193318.PubMedPubMedCentral
305.
go back to reference Ueno G, Iwagami Y, Kobayashi S, Mitsufuji S, Yamada D, Tomimaru Y, Akita H, Asaoka T, Noda T, Gotoh K, et al. ACAT-1-regulated cholesteryl ester accumulation modulates gemcitabine resistance in biliary tract cancer. Ann Surg Oncol. 2022;29(5):2899–909.PubMed Ueno G, Iwagami Y, Kobayashi S, Mitsufuji S, Yamada D, Tomimaru Y, Akita H, Asaoka T, Noda T, Gotoh K, et al. ACAT-1-regulated cholesteryl ester accumulation modulates gemcitabine resistance in biliary tract cancer. Ann Surg Oncol. 2022;29(5):2899–909.PubMed
306.
go back to reference June CH, Riddell SR, Schumacher TN. Adoptive cellular therapy: a race to the finish line. Sci Transl Med. 2015;7(280):280–7. June CH, Riddell SR, Schumacher TN. Adoptive cellular therapy: a race to the finish line. Sci Transl Med. 2015;7(280):280–7.
307.
go back to reference Sanmamed MF, Chen L. A paradigm shift in cancer immunotherapy: from enhancement to normalization. Cell. 2018;175(2):313–26.PubMedPubMedCentral Sanmamed MF, Chen L. A paradigm shift in cancer immunotherapy: from enhancement to normalization. Cell. 2018;175(2):313–26.PubMedPubMedCentral
308.
go back to reference Chowdhury PS, Chamoto K, Honjo T. Combination therapy strategies for improving PD-1 blockade efficacy: a new era in cancer immunotherapy. J Intern Med. 2018;283(2):110–20.PubMed Chowdhury PS, Chamoto K, Honjo T. Combination therapy strategies for improving PD-1 blockade efficacy: a new era in cancer immunotherapy. J Intern Med. 2018;283(2):110–20.PubMed
309.
go back to reference Yang Y, Hsu JM, Sun L, Chan LC, Li CW, Hsu JL, Wei Y, Xia W, Hou J, Qiu Y, et al. Palmitoylation stabilizes PD-L1 to promote breast tumor growth. Cell Res. 2019;29(1):83–6.PubMed Yang Y, Hsu JM, Sun L, Chan LC, Li CW, Hsu JL, Wei Y, Xia W, Hou J, Qiu Y, et al. Palmitoylation stabilizes PD-L1 to promote breast tumor growth. Cell Res. 2019;29(1):83–6.PubMed
310.
go back to reference Yao H, Lan J, Li C, Shi H, Brosseau JP, Wang H, Lu H, Fang C, Zhang Y, Liang L, et al. Inhibiting PD-L1 palmitoylation enhances T-cell immune responses against tumours. Nat Biomed Eng. 2019;3(4):306–17.PubMed Yao H, Lan J, Li C, Shi H, Brosseau JP, Wang H, Lu H, Fang C, Zhang Y, Liang L, et al. Inhibiting PD-L1 palmitoylation enhances T-cell immune responses against tumours. Nat Biomed Eng. 2019;3(4):306–17.PubMed
311.
go back to reference Cantini L, Pecci F, Hurkmans DP, Belderbos RA, Lanese A, Copparoni C, Aerts S, Cornelissen R, Dumoulin DW, Fiordoliva I, et al. High-intensity statins are associated with improved clinical activity of PD-1 inhibitors in malignant pleural mesothelioma and advanced non-small cell lung cancer patients. Eur J Cancer. 2021;144:41–8.PubMed Cantini L, Pecci F, Hurkmans DP, Belderbos RA, Lanese A, Copparoni C, Aerts S, Cornelissen R, Dumoulin DW, Fiordoliva I, et al. High-intensity statins are associated with improved clinical activity of PD-1 inhibitors in malignant pleural mesothelioma and advanced non-small cell lung cancer patients. Eur J Cancer. 2021;144:41–8.PubMed
312.
go back to reference Jiang N, Xie B, Xiao W, Fan M, Xu S, Duan Y, Hamsafar Y, Evans AC, Huang J, Zhou W, et al. Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion. Nat Commun. 2022;13(1):1511.PubMedPubMedCentral Jiang N, Xie B, Xiao W, Fan M, Xu S, Duan Y, Hamsafar Y, Evans AC, Huang J, Zhou W, et al. Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion. Nat Commun. 2022;13(1):1511.PubMedPubMedCentral
313.
go back to reference Wan H, Xu B, Zhu N, Ren B. PGC-1alpha activator-induced fatty acid oxidation in tumor-infiltrating CTLs enhances effects of PD-1 blockade therapy in lung cancer. Tumori. 2020;106(1):55–63.PubMed Wan H, Xu B, Zhu N, Ren B. PGC-1alpha activator-induced fatty acid oxidation in tumor-infiltrating CTLs enhances effects of PD-1 blockade therapy in lung cancer. Tumori. 2020;106(1):55–63.PubMed
314.
go back to reference Saibil SD, St Paul M, Laister RC, Garcia-Batres CR, Israni-Winger K, Elford AR, Grimshaw N, Robert-Tissot C, Roy DG, Jones RG, et al. Activation of peroxisome proliferator-activated receptors alpha and delta synergizes with inflammatory signals to enhance adoptive cell therapy. Cancer Res. 2019;79(3):445–51.PubMed Saibil SD, St Paul M, Laister RC, Garcia-Batres CR, Israni-Winger K, Elford AR, Grimshaw N, Robert-Tissot C, Roy DG, Jones RG, et al. Activation of peroxisome proliferator-activated receptors alpha and delta synergizes with inflammatory signals to enhance adoptive cell therapy. Cancer Res. 2019;79(3):445–51.PubMed
315.
go back to reference Kansal V, Burnham AJ, Kinney BLC, Saba NF, Paulos C, Lesinski GB, Buchwald ZS, Schmitt NC. Statin drugs enhance responses to immune checkpoint blockade in head and neck cancer models. J Immunother Cancer. 2023;11(1):e005940.PubMedPubMedCentral Kansal V, Burnham AJ, Kinney BLC, Saba NF, Paulos C, Lesinski GB, Buchwald ZS, Schmitt NC. Statin drugs enhance responses to immune checkpoint blockade in head and neck cancer models. J Immunother Cancer. 2023;11(1):e005940.PubMedPubMedCentral
316.
go back to reference Takada K, Shimokawa M, Takamori S, Shimamatsu S, Hirai F, Tagawa T, Okamoto T, Hamatake M, Tsuchiya-Kawano Y, Otsubo K, et al. A propensity score-matched analysis of the impact of statin therapy on the outcomes of patients with non-small-cell lung cancer receiving anti-PD-1 monotherapy: a multicenter retrospective study. BMC Cancer. 2022;22(1):503.PubMedPubMedCentral Takada K, Shimokawa M, Takamori S, Shimamatsu S, Hirai F, Tagawa T, Okamoto T, Hamatake M, Tsuchiya-Kawano Y, Otsubo K, et al. A propensity score-matched analysis of the impact of statin therapy on the outcomes of patients with non-small-cell lung cancer receiving anti-PD-1 monotherapy: a multicenter retrospective study. BMC Cancer. 2022;22(1):503.PubMedPubMedCentral
317.
go back to reference Liu X, Bao X, Hu M, Chang H, Jiao M, Cheng J, Xie L, Huang Q, Li F, Li CY. Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer. Nature. 2020;588(7839):693–8.PubMedPubMedCentral Liu X, Bao X, Hu M, Chang H, Jiao M, Cheng J, Xie L, Huang Q, Li F, Li CY. Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer. Nature. 2020;588(7839):693–8.PubMedPubMedCentral
318.
go back to reference Schmidt NM, Wing PAC, Diniz MO, Pallett LJ, Swadling L, Harris JM, Burton AR, Jeffery-Smith A, Zakeri N, Amin OE, et al. Targeting human Acyl-CoA: cholesterol acyltransferase as a dual viral and T cell metabolic checkpoint. Nat Commun. 2021;12(1):2814.PubMedPubMedCentral Schmidt NM, Wing PAC, Diniz MO, Pallett LJ, Swadling L, Harris JM, Burton AR, Jeffery-Smith A, Zakeri N, Amin OE, et al. Targeting human Acyl-CoA: cholesterol acyltransferase as a dual viral and T cell metabolic checkpoint. Nat Commun. 2021;12(1):2814.PubMedPubMedCentral
319.
go back to reference Giro-Perafita A, Palomeras S, Lum DH, Blancafort A, Vinas G, Oliveras G, Perez-Bueno F, Sarrats A, Welm AL, Puig T. Preclinical evaluation of fatty acid synthase and EGFR inhibition in triple-negative breast cancer. Clin Cancer Res. 2016;22(18):4687–97.PubMed Giro-Perafita A, Palomeras S, Lum DH, Blancafort A, Vinas G, Oliveras G, Perez-Bueno F, Sarrats A, Welm AL, Puig T. Preclinical evaluation of fatty acid synthase and EGFR inhibition in triple-negative breast cancer. Clin Cancer Res. 2016;22(18):4687–97.PubMed
320.
go back to reference Li CF, Fang FM, Chen YY, Liu TT, Chan TC, Yu SC, Chen LT, Huang HY. Overexpressed fatty acid synthase in gastrointestinal stromal tumors: targeting a progression-associated metabolic driver enhances the antitumor effect of imatinib. Clin Cancer Res. 2017;23(16):4908–18.PubMed Li CF, Fang FM, Chen YY, Liu TT, Chan TC, Yu SC, Chen LT, Huang HY. Overexpressed fatty acid synthase in gastrointestinal stromal tumors: targeting a progression-associated metabolic driver enhances the antitumor effect of imatinib. Clin Cancer Res. 2017;23(16):4908–18.PubMed
321.
go back to reference Li X, Wu JB, Chung LW, Huang WC. Anti-cancer efficacy of SREBP inhibitor, alone or in combination with docetaxel, in prostate cancer harboring p53 mutations. Oncotarget. 2015;6(38):41018–32.PubMedPubMedCentral Li X, Wu JB, Chung LW, Huang WC. Anti-cancer efficacy of SREBP inhibitor, alone or in combination with docetaxel, in prostate cancer harboring p53 mutations. Oncotarget. 2015;6(38):41018–32.PubMedPubMedCentral
322.
go back to reference Shim JK, Choi S, Yoon SJ, Choi RJ, Park J, Lee EH, Cho HJ, Lee S, Teo WY, Moon JH, et al. Etomoxir, a carnitine palmitoyltransferase 1 inhibitor, combined with temozolomide reduces stemness and invasiveness in patient-derived glioblastoma tumorspheres. Cancer Cell Int. 2022;22(1):309.PubMedPubMedCentral Shim JK, Choi S, Yoon SJ, Choi RJ, Park J, Lee EH, Cho HJ, Lee S, Teo WY, Moon JH, et al. Etomoxir, a carnitine palmitoyltransferase 1 inhibitor, combined with temozolomide reduces stemness and invasiveness in patient-derived glioblastoma tumorspheres. Cancer Cell Int. 2022;22(1):309.PubMedPubMedCentral
323.
go back to reference Han S, Wei R, Zhang X, Jiang N, Fan M, Huang JH, Xie B, Zhang L, Miao W, Butler AC, et al. CPT1A/2-mediated FAO enhancement-a metabolic target in radioresistant breast cancer. Front Oncol. 2019;9:1201.PubMedPubMedCentral Han S, Wei R, Zhang X, Jiang N, Fan M, Huang JH, Xie B, Zhang L, Miao W, Butler AC, et al. CPT1A/2-mediated FAO enhancement-a metabolic target in radioresistant breast cancer. Front Oncol. 2019;9:1201.PubMedPubMedCentral
324.
go back to reference Mao S, Ling Q, Pan J, Li F, Huang S, Ye W, Wei W, Lin X, Qian Y, Wang Y, et al. Inhibition of CPT1a as a prognostic marker can synergistically enhance the antileukemic activity of ABT199. J Transl Med. 2021;19(1):181.PubMedPubMedCentral Mao S, Ling Q, Pan J, Li F, Huang S, Ye W, Wei W, Lin X, Qian Y, Wang Y, et al. Inhibition of CPT1a as a prognostic marker can synergistically enhance the antileukemic activity of ABT199. J Transl Med. 2021;19(1):181.PubMedPubMedCentral
325.
go back to reference Bandyopadhyay S, Li J, Traer E, Tyner JW, Zhou A, Oh ST, Cheng JX. Cholesterol esterification inhibition and imatinib treatment synergistically inhibit growth of BCR-ABL mutation-independent resistant chronic myelogenous leukemia. PLoS ONE. 2017;12(7): e0179558.PubMedPubMedCentral Bandyopadhyay S, Li J, Traer E, Tyner JW, Zhou A, Oh ST, Cheng JX. Cholesterol esterification inhibition and imatinib treatment synergistically inhibit growth of BCR-ABL mutation-independent resistant chronic myelogenous leukemia. PLoS ONE. 2017;12(7): e0179558.PubMedPubMedCentral
326.
go back to reference Lei J, Wang H, Zhu D, Wan Y, Yin L. Combined effects of avasimibe immunotherapy, doxorubicin chemotherapy, and metal-organic frameworks nanoparticles on breast cancer. J Cell Physiol. 2020;235(5):4814–23.PubMed Lei J, Wang H, Zhu D, Wan Y, Yin L. Combined effects of avasimibe immunotherapy, doxorubicin chemotherapy, and metal-organic frameworks nanoparticles on breast cancer. J Cell Physiol. 2020;235(5):4814–23.PubMed
Metadata
Title
Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics
Authors
Hao-Ran Jin
Jin Wang
Zi-Jing Wang
Ming-Jia Xi
Bi-Han Xia
Kai Deng
Jin-Lin Yang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2023
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-023-01498-2

Other articles of this Issue 1/2023

Journal of Hematology & Oncology 1/2023 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine