Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2022

Open Access 01-12-2022 | Review

TGF-β signaling in the tumor metabolic microenvironment and targeted therapies

Authors: Xueke Shi, Jin Yang, Shuzhi Deng, Hongdan Xu, Deyang Wu, Qingxiang Zeng, Shimeng Wang, Tao Hu, Fanglong Wu, Hongmei Zhou

Published in: Journal of Hematology & Oncology | Issue 1/2022

Login to get access

Abstract

Transforming growth factor-β (TGF-β) signaling has a paradoxical role in cancer progression, and it acts as a tumor suppressor in the early stages but a tumor promoter in the late stages of cancer. Once cancer cells are generated, TGF-β signaling is responsible for the orchestration of the immunosuppressive tumor microenvironment (TME) and supports cancer growth, invasion, metastasis, recurrence, and therapy resistance. These progressive behaviors are driven by an “engine” of the metabolic reprogramming in cancer. Recent studies have revealed that TGF-β signaling regulates cancer metabolic reprogramming and is a metabolic driver in the tumor metabolic microenvironment (TMME). Intriguingly, TGF-β ligands act as an “endocrine” cytokine and influence host metabolism. Therefore, having insight into the role of TGF-β signaling in the TMME is instrumental for acknowledging its wide range of effects and designing new cancer treatment strategies. Herein, we try to illustrate the concise definition of TMME based on the published literature. Then, we review the metabolic reprogramming in the TMME and elaborate on the contribution of TGF-β to metabolic rewiring at the cellular (intracellular), tissular (intercellular), and organismal (cancer-host) levels. Furthermore, we propose three potential applications of targeting TGF-β-dependent mechanism reprogramming, paving the way for TGF-β-related antitumor therapy from the perspective of metabolism.
Literature
1.
Yeh HW, Lee SS, Chang CY, Lang YD, Jou YS. A new switch for TGFβ in cancer. Cancer Res. 2019;79(15):3797–805.PubMedCrossRef
2.
Davis MD, Suzaki I, Kawano S, Komiya K, Cai Q, Oh Y, Rubin BK. Tissue factor facilitates wound healing in human airway epithelial cells. Chest. 2019;155(3):534–9.PubMedCrossRef
3.
4.
5.
6.
7.
Kaplan DH, Li MO, Jenison MC, Shlomchik WD, Flavell RA, Shlomchik MJ. Autocrine/paracrine TGFbeta1 is required for the development of epidermal langerhans cells. J Exp Med. 2007;204(11):2545–52.PubMedPubMedCentralCrossRef
8.
Wu F, Weigel KJ, Zhou H, Wang XJ. Paradoxical roles of TGF-β signaling in suppressing and promoting squamous cell carcinoma. Acta Biochim Biophys Sin. 2018;50(1):98–105.PubMedCrossRef
9.
10.
Shi X, Young CD, Zhou H, Wang X. Transforming growth factor-β signaling in fibrotic diseases and cancer-associated fibroblasts. Biomolecules. 2020;10(12):1666.PubMedCentralCrossRef
11.
12.
Bagati A, Kumar S, Jiang P, Pyrdol J, Zou AE, Godicelj A, Mathewson ND, Cartwright ANR, Cejas P, Brown M, et al. Integrin αvβ6-TGFβ-SOX4 pathway drives immune evasion in triple-negative breast cancer. Cancer Cell. 2021;39(1):54-67.e59.PubMedCrossRef
13.
14.
15.
16.
Guido C, Whitaker-Menezes D, Capparelli C, Balliet R, Lin Z, Pestell RG, Howell A, Aquila S, Andò S, Martinez-Outschoorn U, et al. Metabolic reprogramming of cancer-associated fibroblasts by TGF-β drives tumor growth: connecting TGF-β signaling with “Warburg-like” cancer metabolism and L-lactate production. Cell Cycle. 2012;11(16):3019–35 (Georgetown, Tex).PubMedPubMedCentralCrossRef
17.
Fosslien E. Cancer morphogenesis: role of mitochondrial failure. Ann Clin Lab Sci. 2008;38(4):307–29.PubMed
18.
Wang YA, Li XL, Mo YZ, Fan CM, Tang L, Xiong F, Guo C, Xiang B, Zhou M, Ma J, et al. Effects of tumor metabolic microenvironment on regulatory T cells. Mol Cancer. 2018;17(1):168.PubMedPubMedCentralCrossRef
19.
20.
Eisenberg L, Eisenberg-Bord M, Eisenberg-Lerner A, Sagi-Eisenberg R. Metabolic alterations in the tumor microenvironment and their role in oncogenesis. Cancer Lett. 2020;484:65–71.PubMedCrossRef
21.
22.
Magalhaes I, Yogev O, Mattsson J, Schurich A. The metabolic profile of tumor and virally infected cells shapes their microenvironment counteracting T Cell immunity. Front Immunol. 2019;10:2309.PubMedPubMedCentralCrossRef
23.
Yang E, Wang X, Gong Z, Yu M, Wu H, Zhang D. Exosome-mediated metabolic reprogramming: the emerging role in tumor microenvironment remodeling and its influence on cancer progression. Signal Transduct Target Ther. 2020;5(1):242.PubMedPubMedCentralCrossRef
24.
Li X, Wenes M, Romero P, Huang SC, Fendt SM, Ho PC. Navigating metabolic pathways to enhance antitumour immunity and immunotherapy. Nat Rev Clin Oncol. 2019;16(7):425–41.PubMedCrossRef
25.
26.
27.
Hua W, Ten Dijke P, Kostidis S, Giera M, Hornsveld M. TGFβ-induced metabolic reprogramming during epithelial-to-mesenchymal transition in cancer. Cellular Mol Life Sci: CMLS. 2020;77(11):2103–23.PubMedCrossRef
28.
29.
Ocaña MC, Martínez-Poveda B, Quesada AR, Medina M. Metabolism within the tumor microenvironment and its implication on cancer progression: an ongoing therapeutic target. Med Res Rev. 2019;39(1):70–113.PubMedCrossRef
30.
31.
32.
33.
Deng S, Wang S, Shi X, Zhou H. Microenvironment in oral potentially malignant disorders: multi-dimensional characteristics and mechanisms of carcinogenesis. Int J Mol Sci. 2022;23(16):8940.PubMedPubMedCentralCrossRef
34.
Koundouros N, Poulogiannis G. Reprogramming of fatty acid metabolism in cancer. Br J Cancer. 2020;122(1):4–22.PubMedCrossRef
35.
36.
Gupta S, Roy A, Dwarakanath BS. Metabolic cooperation and competition in the tumor microenvironment: implications for therapy. Front Oncol. 2017;7:68–68.PubMedPubMedCentralCrossRef
37.
Shen W, Tao G-Q, Zhang Y, Cai B, Sun J, Tian Z-Q. TGF-β in pancreatic cancer initiation and progression: two sides of the same coin. Cell Biosci. 2017;7(1):39.PubMedPubMedCentralCrossRef
38.
Penafuerte C, Bautista-Lopez N, Bouchentouf M, Birman E, Forner K, Galipeau J. Novel TGF-β antagonist inhibits tumor growth and angiogenesis by inducing IL-2 receptor-driven STAT1 activation. J Immunol. 2011;186(12):6933–44.PubMedCrossRef
39.
Xie F, Ling L, van Dam H, Zhou F, Zhang L. TGF-β signaling in cancer metastasis. Acta Biochim Biophys Sin. 2018;50(1):121–32.PubMedCrossRef
40.
41.
Angioni R, Sánchez-Rodríguez R, Viola A, Molon B. TGF-β in cancer: metabolic driver of the tolerogenic crosstalk in the tumor microenvironment. Cancers. 2021;13(3):401.PubMedPubMedCentralCrossRef
42.
43.
Weinhouse S. Glycolysis, respiration, and anomalous gene expression in experimental hepatomas: G.H.A Clowes memorial lecture. Cancer Res. 1972;32(10):2007–16.PubMed
44.
45.
Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev Cancer. 2004;4(11):891–9.PubMedCrossRef
46.
Vander Heiden MG, Cantley LC, Thompson CBJ. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930):1029–33.PubMedPubMedCentralCrossRef
47.
Lunt SY, Vander Heiden MG. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol. 2011;27:441–64.PubMedCrossRef
48.
de la Cruz-López KG, Castro-Muñoz LJ, Reyes-Hernández DO, García-Carrancá A, Manzo-Merino J. Lactate in the regulation of tumor microenvironment and therapeutic approaches. Front Oncol. 2019;9:1143.PubMedPubMedCentralCrossRef
49.
Bardella C, Pollard PJ, Tomlinson I. SDH mutations in cancer. Biochem Biophys Acta. 2011;1807(11):1432–43.PubMed
50.
Letouzé E, Martinelli C, Loriot C, Burnichon N, Abermil N, Ottolenghi C, Janin M, Menara M, Nguyen AT, Benit P, et al. SDH mutations establish a hypermethylator phenotype in paraganglioma. Cancer Cell. 2013;23(6):739–52.PubMedCrossRef
51.
Marquez J, Flores J, Kim AH, Nyamaa B, Nguyen ATT, Park N, Han J. Rescue of TCA cycle dysfunction for cancer therapy. J Clin Med. 2019;8(12):2161.PubMedCentralCrossRef
52.
53.
54.
Feng Q, Li X, Sun W, Sun M, Li Z, Sheng H, Xie F, Zhang S, Shan C. Targeting G6PD reverses paclitaxel resistance in ovarian cancer by suppressing GSTP1. Biochem Pharmacol. 2020;178:114092.PubMedCrossRef
55.
Zhang Q, Han Q, Yang Z, Ni Y, Agbana YL, Bai H, Yi Z, Yi X, Kuang Y, Zhu Y. G6PD facilitates clear cell renal cell carcinoma invasion by enhancing MMP2 expression through ROS-MAPK axis pathway. Int J Oncol. 2020;57(1):197–212.PubMedPubMedCentral
56.
Yamawaki K, Mori Y, Sakai H, Kanda Y, Shiokawa D, Ueda H, Ishiguro T, Yoshihara K, Nagasaka K, Onda T, et al. Integrative analyses of gene expression and chemosensitivity of patient-derived ovarian cancer spheroids link G6PD-driven redox metabolism to cisplatin chemoresistance. Cancer Lett. 2021;521:29–38.PubMedCrossRef
57.
Hong W, Cai P, Xu C, Cao D, Yu W, Zhao Z, Huang M, Jin J. Inhibition of glucose-6-phosphate dehydrogenase reverses cisplatin resistance in lung cancer cells via the redox system. Front Pharmacol. 2018;9:43.PubMedPubMedCentralCrossRef
58.
Schmidt M, Voelker HU, Kapp M, Krockenberger M, Dietl J, Kammerer U. Glycolytic phenotype in breast cancer: activation of Akt, up-regulation of GLUT1, TKTL1 and down-regulation of M2PK. J Cancer Res Clin Oncol. 2010;136(2):219–25.PubMedCrossRef
59.
da Costa IA, Hennenlotter J, Stühler V, Kühs U, Scharpf M, Todenhöfer T, Stenzl A, Bedke J. Transketolase like 1 (TKTL1) expression alterations in prostate cancer tumorigenesis. Urol Oncol. 2018;36(10):472.e421-472.e427.CrossRef
60.
Schultz H, Kähler D, Branscheid D, Vollmer E, Zabel P, Goldmann T. TKTL1 is overexpressed in a large portion of non-small cell lung cancer specimens. Diagn Pathol. 2008;3(1):35.PubMedPubMedCentralCrossRef
61.
Wang C, Guo K, Gao D, Kang X, Jiang K, Li Y, Sun L, Zhang S, Sun C, Liu X, et al. Identification of transaldolase as a novel serum biomarker for hepatocellular carcinoma metastasis using xenografted mouse model and clinic samples. Cancer Lett. 2011;313(2):154–66.PubMedCrossRef
62.
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.PubMedPubMedCentralCrossRef
63.
Gounaris I, Brenton JD. Molecular pathogenesis of ovarian clear cell carcinoma. Future Oncol. 2015;11(9):1389–405 (London, England).PubMedCrossRef
64.
Pletneva MA, Andea A, Palanisamy N, Betz BL, Carskadon S, Wang M, Patel RM, Fullen DR, Harms PW. Clear cell melanoma: a cutaneous clear cell malignancy. Arch Pathol Lab Med. 2014;138(10):1328–36.PubMedCrossRef
65.
Pescador N, Villar D, Cifuentes D, Garcia-Rocha M, Ortiz-Barahona A, Vazquez S, Ordoñez A, Cuevas Y, Saez-Morales D, Garcia-Bermejo ML, et al. Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1. PLoS ONE. 2010;5(3):e9644.PubMedPubMedCentralCrossRef
66.
Shen GM, Zhang FL, Liu XL, Zhang JW. Hypoxia-inducible factor 1-mediated regulation of PPP1R3C promotes glycogen accumulation in human MCF-7 cells under hypoxia. FEBS Lett. 2010;584(20):4366–72.PubMedCrossRef
67.
Pelletier J, Bellot G, Gounon P, Lacas-Gervais S, Pouysségur J, Mazure NM. Glycogen synthesis is induced in hypoxia by the hypoxia-inducible factor and promotes cancer cell survival. Front Oncol. 2012;2:18.PubMedPubMedCentralCrossRef
68.
Iida Y, Aoki K, Asakura T, Ueda K, Yanaihara N, Takakura S, Yamada K, Okamoto A, Tanaka T, Ohkawa K. Hypoxia promotes glycogen synthesis and accumulation in human ovarian clear cell carcinoma. Int J Oncol. 2012;40(6):2122–30.PubMed
69.
70.
Liu Q, Li J, Zhang W, Xiao C, Zhang S, Nian C, Li J, Su D, Chen L, Zhao Q, et al. Glycogen accumulation and phase separation drives liver tumor initiation. Cell. 2021;184(22):5559-5576.e19.PubMedCrossRef
71.
Favaro E, Bensaad K, Chong MG, Tennant DA, Ferguson DJ, Snell C, Steers G, Turley H, Li JL, Günther UL, et al. Glucose utilization via glycogen phosphorylase sustains proliferation and prevents premature senescence in cancer cells. Cell Metab. 2012;16(6):751–64.PubMedCrossRef
72.
Pastushenko I, Blanpain C. EMT transition states during tumor progression and metastasis. Trends Cell Biol. 2019;29(3):212–26.PubMedCrossRef
73.
Xue G, Restuccia DF, Lan Q, Hynx D, Dirnhofer S, Hess D, Rüegg C, Hemmings BA. Akt/PKB-mediated phosphorylation of Twist1 promotes tumor metastasis via mediating cross-talk between PI3K/Akt and TGF-β signaling axes. Cancer Discov. 2012;2(3):248–59.PubMedCrossRef
74.
Brandl M, Seidler B, Haller F, Adamski J, Schmid RM, Saur D, Schneider G. IKK(α) controls canonical TGF(ß)-SMAD signaling to regulate genes expressing SNAIL and SLUG during EMT in panc1 cells. J Cell Sci. 2010;123(Pt 24):4231–9.PubMedCrossRef
75.
Zhang L, Wang X, Lai C, Zhang H, Lai M. PMEPA1 induces EMT via a non-canonical TGF-β signalling in colorectal cancer. J Cell Mol Med. 2019;23(5):3603–15.PubMedPubMedCentralCrossRef
76.
Li W, Wei Z, Liu Y, Li H, Ren R, Tang Y. Increased 18F-FDG uptake and expression of Glut1 in the EMT transformed breast cancer cells induced by TGF-beta. Neoplasma. 2010;57(3):234–40.PubMedCrossRef
77.
Liu M, Quek LE, Sultani G, Turner N. Epithelial-mesenchymal transition induction is associated with augmented glucose uptake and lactate production in pancreatic ductal adenocarcinoma. Cancer Metab. 2016;4:19.PubMedPubMedCentralCrossRef
78.
Nilchian A, Giotopoulou N, Sun W, Fuxe J. Different regulation of Glut1 expression and glucose uptake during the induction and chronic stages of TGFβ1-induced EMT in breast cancer cells. Biomolecules. 2020;10(12):1621.PubMedCentralCrossRef
79.
Dai H, Deng HB, Wang YH, Guo JJ. Resveratrol inhibits the growth of gastric cancer via the Wnt/β-catenin pathway. Oncol Lett. 2018;16(2):1579–83.PubMedPubMedCentral
80.
Oh S, Kim H, Nam K, Shin I. Silencing of Glut1 induces chemoresistance via modulation of Akt/GSK-3β/β-catenin/survivin signaling pathway in breast cancer cells. Arch Biochem Biophys. 2017;636:110–22.PubMedCrossRef
81.
Masin M, Vazquez J, Rossi S, Groeneveld S, Samson N, Schwalie PC, Deplancke B, Frawley LE, Gouttenoire J, Moradpour D, et al. GLUT3 is induced during epithelial-mesenchymal transition and promotes tumor cell proliferation in non-small cell lung cancer. Cancer Metab. 2014;2:11.PubMedPubMedCentralCrossRef
82.
Botzer LE, Maman S, Sagi-Assif O, Meshel T, Nevo I, Yron I, Witz IP. Hexokinase 2 is a determinant of neuroblastoma metastasis. Br J Cancer. 2016;114(7):759–66.PubMedCrossRef
83.
Chen J, Yu Y, Li H, Hu Q, Chen X, He Y, Xue C, Ren F, Ren Z, Li J, et al. Long non-coding RNA PVT1 promotes tumor progression by regulating the miR-143/HK2 axis in gallbladder cancer. Mol Cancer. 2019;18(1):33.PubMedPubMedCentralCrossRef
84.
Rodríguez-García A, Samsó P, Fontova P, Simon-Molas H, Manzano A, Castaño E, Rosa JL, Martinez-Outshoorn U, Ventura F, Navarro-Sabaté À, et al. TGF-β1 targets Smad, p38 MAPK, and PI3K/Akt signaling pathways to induce PFKFB3 gene expression and glycolysis in glioblastoma cells. FEBS J. 2017;284(20):3437–54.PubMedCrossRef
85.
De Bock K, Georgiadou M, Schoors S, Kuchnio A, Wong BW, Cantelmo AR, Quaegebeur A, Ghesquière B, Cauwenberghs S, Eelen G, et al. Role of PFKFB3-driven glycolysis in vessel sprouting. Cell. 2013;154(3):651–63.PubMedCrossRef
86.
Van Schaftingen E, Lederer B, Bartrons R, Hers HG. A kinetic study of pyrophosphate: fructose-6-phosphate phosphotransferase from potato tubers. Application to a microassay of fructose 2,6-bisphosphate. Eur J Biochem. 1982;129(1):191–5.PubMedCrossRef
87.
Yalcin A, Solakoglu TH, Ozcan SC, Guzel S, Peker S, Celikler S, Balaban BD, Sevinc E, Gurpinar Y, Chesney JA. 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase-3 is required for transforming growth factor β1-enhanced invasion of Panc1 cells in vitro. Biochem Biophys Res Commun. 2017;484(3):687–93.PubMedCrossRef
88.
89.
Hamabe A, Konno M, Tanuma N, Shima H, Tsunekuni K, Kawamoto K, Nishida N, Koseki J, Mimori K, Gotoh N, et al. Role of pyruvate kinase M2 in transcriptional regulation leading to epithelial-mesenchymal transition. Proc Natl Acad Sci USA. 2014;111(43):15526–31.PubMedPubMedCentralCrossRef
90.
Liu Y, Yuan X, Li W, Cao Q, Shu Y. Aspirin-triggered resolvin D1 inhibits TGF-β1-induced EMT through the inhibition of the mTOR pathway by reducing the expression of PKM2 and is closely linked to oxidative stress. Int J Mol Med. 2016;38(4):1235–42.PubMedCrossRef
91.
Vander Heiden MG, Christofk HR, Schuman E, Subtelny AO, Sharfi H, Harlow EE, Xian J, Cantley LC. Identification of small molecule inhibitors of pyruvate kinase M2. Biochem Pharmacol. 2010;79(8):1118–24.PubMedCrossRef
92.
Chen J, Xie J, Jiang Z, Wang B, Wang Y, Hu X. Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2. Oncogene. 2011;30(42):4297–306.PubMedCrossRef
93.
Shankar Babu M, Mahanta S, Lakhter AJ, Hato T, Paul S, Naidu SR. Lapachol inhibits glycolysis in cancer cells by targeting pyruvate kinase M2. PLoS ONE. 2018;13(2):e0191419.PubMedPubMedCentralCrossRef
94.
Li X, Zhang Z, Zhang Y, Cao Y, Wei H, Wu Z. Upregulation of lactate-inducible snail protein suppresses oncogene-mediated senescence through p16(INK4a) inactivation. J Exp Clin Cancer Res: CR. 2018;37(1):39–39.PubMedPubMedCentralCrossRef
95.
Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M, Gottfried E, Schwarz S, Rothe G, Hoves S, et al. Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood. 2007;109(9):3812–9.PubMedCrossRef
96.
Wang H, Chen Y, Wu G. SDHB deficiency promotes TGFβ-mediated invasion and metastasis of colorectal cancer through transcriptional repression complex SNAIL1-SMAD3/4. Transl oncology. 2016;9(6):512–20.CrossRef
97.
Aspuria PP, Lunt SY, Väremo L, Vergnes L, Gozo M, Beach JA, Salumbides B, Reue K, Wiedemeyer WR, Nielsen J, et al. Succinate dehydrogenase inhibition leads to epithelial-mesenchymal transition and reprogrammed carbon metabolism. Cancer Metabol. 2014;2:21.CrossRef
98.
Soukupova J, Malfettone A, Hyroššová P, Hernández-Alvarez M-I, Peñuelas-Haro I, Bertran E, Junza A, Capellades J, Giannelli G, Yanes O, et al. Role of the transforming growth factor-β in regulating hepatocellular carcinoma oxidative metabolism. Sci Rep. 2017;7(1):12486–12486.PubMedPubMedCentralCrossRef
99.
Sun W, Ma Y, Chen P, Wang D. MicroRNA-10a silencing reverses cisplatin resistance in the A549/cisplatin human lung cancer cell line via the transforming growth factor-β/Smad2/STAT3/STAT5 pathway. Mol Med Rep. 2015;11(5):3854–9.PubMedCrossRef
100.
Bissey P-A, Law JH, Bruce JP, Shi W, Renoult A, Chua MLK, Yip KW, Liu F-F. Dysregulation of the MiR-449b target TGFBI alters the TGFβ pathway to induce cisplatin resistance in nasopharyngeal carcinoma. Oncogenesis. 2018;7(5):40.PubMedPubMedCentralCrossRef
101.
Zhang R, Tao F, Ruan S, Hu M, Hu Y, Fang Z, Mei L, Gong C. The TGFβ1-FOXM1-HMGA1-TGFβ1 positive feedback loop increases the cisplatin resistance of non-small cell lung cancer by inducing G6PD expression. Am J Transl Res. 2019;11(11):6860–76.PubMedPubMedCentral
102.
Zeng N, Okumura T, Alauddin M, Khozooei S, Rajaxavier J, Zhang S, Singh Y, Shi B, Brucker SY, Wallwiener D, et al. LEFTY2/endometrial bleeding-associated factor up-regulates Na+ coupled glucose transporter SGLT1 expression and glycogen accumulation in endometrial cancer cells. PLoS ONE. 2020;15(4):e0230044.PubMedPubMedCentralCrossRef
103.
Guo X, Ramirez A, Waddell DS, Li Z, Liu X, Wang XF. Axin and GSK3- control Smad3 protein stability and modulate TGF- signaling. Genes Dev. 2008;22(1):106–20.PubMedPubMedCentralCrossRef
104.
Cozzolino AM, Alonzi T, Santangelo L, Mancone C, Conti B, Steindler C, Musone M, Cicchini C, Tripodi M, Marchetti A. TGFβ overrides HNF4α tumor suppressing activity through GSK3β inactivation: implication for hepatocellular carcinoma gene therapy. J Hepatol. 2013;58(1):65–72.PubMedCrossRef
105.
Matsumoto T, Yokoi A, Hashimura M, Oguri Y, Akiya M, Saegusa M. TGF-β-mediated LEFTY/Akt/GSK-3β/Snail axis modulates epithelial-mesenchymal transition and cancer stem cell properties in ovarian clear cell carcinomas. Mol Carcinog. 2018;57(8):957–67.PubMedCrossRef
106.
Goluszko P, Nowicki B. Membrane cholesterol: a crucial molecule affecting interactions of microbial pathogens with mammalian cells. Infect Immun. 2005;73(12):7791–6.PubMedPubMedCentralCrossRef
107.
Zhao W, Prijic S, Urban BC, Tisza MJ, Zuo Y, Li L, Tan Z, Chen X, Mani SA, Chang JT. Candidate antimetastasis drugs suppress the metastatic capacity of breast cancer cells by reducing membrane fluidity. Can Res. 2016;76(7):2037–49.CrossRef
108.
Baek AE, Yu YA, He S, Wardell SE, Chang CY, Kwon S, Pillai RV, McDowell HB, Thompson JW, Dubois LG, et al. The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells. Nat Commun. 2017;8(1):864.PubMedPubMedCentralCrossRef
109.
Röhrig F, Schulze A. The multifaceted roles of fatty acid synthesis in cancer. Nat Rev Cancer. 2016;16(11):732–49.PubMedCrossRef
110.
Menendez JA, Lupu R. Fatty acid synthase (FASN) as a therapeutic target in breast cancer. Expert Opin Ther Targets. 2017;21(11):1001–16.PubMedCrossRef
111.
Tirinato L, Pagliari F, Limongi T, Marini M, Falqui A, Seco J, Candeloro P, Liberale C, Di Fabrizio E. An overview of lipid droplets in cancer and cancer stem cells. Stem Cells Int. 2017;2017:1656053.PubMedPubMedCentralCrossRef
112.
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-1α contribute to cell growth and survival after hypoxia-reoxygenation. Cell Rep. 2014;9(1):349–65.PubMedCrossRef
113.
Flavin R, Peluso S, Nguyen PL, Loda M. Fatty acid synthase as a potential therapeutic target in cancer. Future Oncol. 2010;6(4):551–62 (London, England).PubMedCrossRef
114.
Xu S, Chen T, Dong L, Li T, Xue H, Gao B, Ding X, Wang H, Li H. Fatty acid synthase promotes breast cancer metastasis by mediating changes in fatty acid metabolism. Oncol Lett. 2021;21(1):27–27.PubMed
115.
Aiderus A, Black MA, Dunbier AK. Fatty acid oxidation is associated with proliferation and prognosis in breast and other cancers. BMC Cancer. 2018;18(1):805.PubMedPubMedCentralCrossRef
116.
Mozolewska P, Duzowska K, Pakiet A, Mika A, ŚledziŃski T. Inhibitors of fatty acid synthesis and oxidation as potential anticancer agents in colorectal cancer treatment. Anticancer Res. 2020;40(9):4843–56.PubMedCrossRef
117.
Chen M, Zhao Y, Yang X, Zhao Y, Liu Q, Liu Y, Hou Y, Sun H, Jin W. NSDHL promotes triple-negative breast cancer metastasis through the TGFβ signaling pathway and cholesterol biosynthesis. Breast Cancer Res Treat. 2021;187(2):349–62.PubMedCrossRef
118.
Di Guglielmo GM, Le Roy C, Goodfellow AF, Wrana JL. Distinct endocytic pathways regulate TGF-beta receptor signalling and turnover. Nat Cell Biol. 2003;5(5):410–21.PubMedCrossRef
119.
Hayes S, Chawla A, Corvera S. TGF beta receptor internalization into EEA1-enriched early endosomes: role in signaling to Smad2. J Cell Biol. 2002;158(7):1239–49.PubMedPubMedCentralCrossRef
120.
121.
Gabitova-Cornell L, Surumbayeva A, Peri S, Franco-Barraza J, Restifo D, Weitz N, Ogier C, Goldman AR, Hartman TR, Francescone R, et al. Cholesterol pathway inhibition induces TGF-β signaling to promote Basal differentiation in pancreatic cancer. Cancer Cell. 2020;38(4):567-583.e511.PubMedPubMedCentralCrossRef
122.
Chen C-L, Huang SS, Huang JS. Cholesterol modulates cellular TGF-beta responsiveness by altering TGF-beta binding to TGF-beta receptors. J Cell Physiol. 2008;215(1):223–33.PubMedPubMedCentralCrossRef
123.
Zhao Z, Hao D, Wang L, Li J, Meng Y, Li P, Wang Y, Zhang C, Zhou H, Gardner K, et al. CtBP promotes metastasis of breast cancer through repressing cholesterol and activating TGF-β signaling. Oncogene. 2019;38(12):2076–91.PubMedCrossRef
124.
Xue L, Qi H, Zhang H, Ding L, Huang Q, Zhao D, Wu BJ, Li X. Targeting SREBP-2-regulated mevalonate metabolism for cancer therapy. Front Oncol. 2020;10:1510.PubMedPubMedCentralCrossRef
125.
Mullen GE, Yet L. Progress in the development of fatty acid synthase inhibitors as anticancer targets. Bioorg Med Chem Lett. 2015;25(20):4363–9.PubMedCrossRef
126.
Yang L, Zhang F, Wang X, Tsai Y, Chuang K-H, Keng PC, Lee SO, Chen Y. A FASN-TGF-β1-FASN regulatory loop contributes to high EMT/metastatic potential of cisplatin-resistant non-small cell lung cancer. Oncotarget. 2016;7(34):55543–54.PubMedPubMedCentralCrossRef
127.
Liu QQ, Huo HY, Ao S, Liu T, Yang L, Fei ZY, Zhang ZQ, Ding L, Cui QH, Lin J, et al. TGF-β1-induced epithelial-mesenchymal transition increases fatty acid oxidation and OXPHOS activity via the p-AMPK pathway in breast cancer cells. Oncol Rep. 2020;44(3):1206–15.PubMedCrossRef
128.
Damaghi M, Gillies R. Phenotypic changes of acid-adapted cancer cells push them toward aggressiveness in their evolution in the tumor microenvironment. Cell Cycle. 2017;16(19):1739–43 (Georgetown, Tex).PubMedCrossRef
129.
Corbet C, Feron O. Tumour acidosis: from the passenger to the driver’s seat. Nat Rev Cancer. 2017;17(10):577–93.PubMedCrossRef
130.
131.
Corbet C, Bastien E, de Santiago Jesus JP, Dierge E, Martherus R, Vander Linden C, Doix B, Degavre C, Guilbaud C, Petit L, et al. TGFβ2-induced formation of lipid droplets supports acidosis-driven EMT and the metastatic spreading of cancer cells. Nat Commun. 2020;11(1):454.PubMedPubMedCentralCrossRef
132.
Vučetić M, Cormerais Y, Parks SK, Pouysségur J. The central role of amino acids in cancer redox homeostasis: vulnerability points of the cancer redox code. Front Oncol. 2017;7:319.PubMedPubMedCentralCrossRef
133.
Matés JM, Pérez-Gómez C, de Núñez CI, Asenjo M, Márquez J. Glutamine and its relationship with intracellular redox status, oxidative stress and cell proliferation/death. Int J Biochem Cell Biol. 2002;34(5):439–58.PubMedCrossRef
134.
Li Z, Zhang H. Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression. Cell Mol Life Sci: CMLS. 2016;73(2):377–92.PubMedCrossRef
135.
Togashi Y, Arao T, Kato H, Matsumoto K, Terashima M, Hayashi H, de Velasco MA, Fujita Y, Kimura H, Yasuda T, et al. Frequent amplification of ORAOV1 gene in esophageal squamous cell cancer promotes an aggressive phenotype via proline metabolism and ROS production. Oncotarget. 2014;5(10):2962–73.PubMedCrossRef
136.
Scott L, Lamb J, Smith S, Wheatley DN. Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignant cells. Br J Cancer. 2000;83(6):800–10.PubMedPubMedCentralCrossRef
137.
Nakasuka F, Tabata S, Sakamoto T, Hirayama A, Ebi H, Yamada T, Umetsu K, Ohishi M, Ueno A, Goto H, et al. TGF-β-dependent reprogramming of amino acid metabolism induces epithelial–mesenchymal transition in non-small cell lung cancers. Commun Biol. 2021;4(1):782.PubMedPubMedCentralCrossRef
138.
Kinugasa H, Whelan KA, Tanaka K, Natsuizaka M, Long A, Guo A, Chang S, Kagawa S, Srinivasan S, Guha M, et al. Mitochondrial SOD2 regulates epithelial–mesenchymal transition and cell populations defined by differential CD44 expression. Oncogene. 2015;34(41):5229–39.PubMedPubMedCentralCrossRef
139.
Hibbs JB Jr, Taintor RR, Vavrin Z. Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science. 1987;235(4787):473–6 (New York, NY).PubMedCrossRef
140.
Xie K, Dong Z, Fidler IJ. Activation of nitric oxide synthase gene for inhibition of cancer metastasis. J Leukoc Biol. 1996;59(6):797–803.PubMedCrossRef
141.
Lejeune P, Lagadec P, Onier N, Pinard D, Ohshima H, Jeannin JF. Nitric oxide involvement in tumor-induced immunosuppression. J Immunol (Baltimore, Md: 1950). 1994;152(10):5077–83.
142.
Lagadec P, Raynal S, Lieubeau B, Onier N, Arnould L, Saint-Giorgio V, Lawrence DA, Jeannin JF. Evidence for control of nitric oxide synthesis by intracellular transforming growth factor-beta1 in tumor cells. Implications for tumor development. Am J Pathol. 1999;154(6):1867–76.PubMedPubMedCentralCrossRef
143.
Wu F, Yang J, Liu J, Wang Y, Mu J, Zeng Q, Deng S, Zhou H. Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer. Signal Transduct Target Ther. 2021;6(1):218.PubMedPubMedCentralCrossRef
144.
Hawinkels LJ, Paauwe M, Verspaget HW, Wiercinska E, van der Zon JM, van der Ploeg K, Koelink PJ, Lindeman JH, Mesker W, ten Dijke P, et al. Interaction with colon cancer cells hyperactivates TGF-β signaling in cancer-associated fibroblasts. Oncogene. 2014;33(1):97–107.PubMedCrossRef
145.
Ringuette Goulet C, Bernard G, Tremblay S, Chabaud S, Bolduc S, Pouliot F. Exosomes induce fibroblast differentiation into cancer-associated fibroblasts through TGFβ signaling. Mol Cancer Res: MCR. 2018;16(7):1196–204.PubMedCrossRef
146.
Untergasser G, Gander R, Lilg C, Lepperdinger G, Plas E, Berger P. Profiling molecular targets of TGF-beta1 in prostate fibroblast-to-myofibroblast transdifferentiation. Mech Ageing Dev. 2005;126(1):59–69.PubMedCrossRef
147.
Lamprecht S, Sigal-Batikoff I, Shany S, Abu-Freha N, Ling E, Delinasios GJ, Moyal-Atias K, Delinasios JG, Fich A. Teaming up for trouble: cancer cells, transforming growth factor-β1 signaling and the epigenetic corruption of stromal naïve fibroblasts. Cancers. 2018;10(3):61.PubMedCentralCrossRef
148.
Lin J, Liu C, Ge L, Gao Q, He X, Liu Y, Li S, Zhou M, Chen Q, Zhou H. Carcinoma-associated fibroblasts promotes the proliferation of a lingual carcinoma cell line by secreting keratinocyte growth factor. Tumour Biol. 2011;32(3):597–602.PubMedCrossRef
149.
Shi X, Luo J, Weigel KJ, Hall SC, Du D, Wu F, Rudolph MC, Zhou H, Young CD, Wang XJ. Cancer-associated fibroblasts facilitate squamous cell carcinoma lung metastasis in Mice by providing TGFβ-mediated cancer stem cell Niche. Front Cell Dev Biol. 2021;9:668164.PubMedPubMedCentralCrossRef
150.
Zhang D, Wang Y, Shi Z, Liu J, Sun P, Hou X, Zhang J, Zhao S, Zhou BP, Mi J. Metabolic reprogramming of cancer-associated fibroblasts by IDH3α downregulation. Cell Rep. 2015;10(8):1335–48.PubMedCrossRef
151.
Roy A, Bera S. CAF cellular glycolysis: linking cancer cells with the microenvironment. Tumour Biol. 2016;37(7):8503–14.PubMedCrossRef
152.
Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, Casimiro MC, Wang C, Fortina P, Addya S, et al. The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle. 2009;8(23):3984–4001 (Georgetown, Tex).PubMedCrossRef
153.
Karuppagounder SS, Ratan RR. Hypoxia-inducible factor prolyl hydroxylase inhibition: robust new target or another big bust for stroke therapeutics? J Cereb Blood Flow Metab. 2012;32(7):1347–61.PubMedPubMedCentralCrossRef
154.
Berra E, Benizri E, Ginouvès A, Volmat V, Roux D, Pouysségur J. HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. EMBO J. 2003;22(16):4082–90.PubMedPubMedCentralCrossRef
155.
156.
Liu Y, Hu T, Shen J, Li SF, Lin JW, Zheng XH, Gao QH, Zhou HM. Separation, cultivation and biological characteristics of oral carcinoma-associated fibroblasts. Oral Dis. 2006;12(4):375–80.PubMedCrossRef
157.
Wu F, Wang S, Zeng Q, Liu J, Yang J, Mu J, Xu H, Wu L, Gao Q, He X, et al. TGF-βRII regulates glucose metabolism in oral cancer-associated fibroblasts via promoting PKM2 nuclear translocation. Cell death discovery. 2022;8(1):3.PubMedPubMedCentralCrossRef
158.
Yang J, Shi X, Yang M, Luo J, Gao Q, Wang X, Wu Y, Tian Y, Wu F, Zhou H. Glycolysis reprogramming in cancer-associated fibroblasts promotes the growth of oral cancer through the lncRNA H19/miR-675-5p/PFKFB3 signaling pathway. Int J Oral Sci. 2021;13(1):12.PubMedPubMedCentralCrossRef
159.
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.PubMedPubMedCentralCrossRef
160.
Meng W, Wu Y, He X, Liu C, Gao Q, Ge L, Wu L, Liu Y, Guo Y, Li X, et al. A systems biology approach identifies effective tumor-stroma common targets for oral squamous cell carcinoma. Can Res. 2014;74(8):2306–15.CrossRef
161.
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.PubMedPubMedCentralCrossRef
162.
Bonuccelli G, Tsirigos A, Whitaker-Menezes D, Pavlides S, Pestell RG, Chiavarina B, Frank PG, Flomenberg N, Howell A, Martinez-Outschoorn UE, et al. Ketones and lactate “fuel” tumor growth and metastasis: evidence that epithelial cancer cells use oxidative mitochondrial metabolism. Cell Cycle. 2010;9(17):3506–14 (Georgetown, Tex).PubMedPubMedCentralCrossRef
163.
Hu L, Xu X, Li Q, Chen X, Yuan X, Qiu S, Yao C, Zhang D, Wang F. Caveolin-1 increases glycolysis in pancreatic cancer cells and triggers cachectic states. FASEB J. 2021;35(8):e21826.PubMedCrossRef
164.
Yang L, Achreja A, Yeung TL, Mangala LS, Jiang D, Han C, Baddour J, Marini JC, Ni J, Nakahara R, et al. Targeting stromal glutamine synthetase in tumors disrupts tumor microenvironment-regulated cancer cell growth. Cell Metab. 2016;24(5):685–700.PubMedPubMedCentralCrossRef
165.
Mestre-Farrera A, Bruch-Oms M, Peña R, Rodríguez-Morató J, Alba-Castellón L, Comerma L, Quintela-Fandino M, Duñach M, Baulida J, Pozo ÓJ, et al. Glutamine-directed migration of cancer-activated fibroblasts facilitates epithelial tumor invasion. Can Res. 2021;81(2):438–51.CrossRef
166.
Martinez-Outschoorn UE, Pavlides S, Howell A, Pestell RG, Tanowitz HB, Sotgia F, Lisanti MP. Stromal-epithelial metabolic coupling in cancer: integrating autophagy and metabolism in the tumor microenvironment. Int J Biochem Cell Biol. 2011;43(7):1045–51.PubMedPubMedCentralCrossRef
167.
Avagliano A, Granato G, Ruocco MR, Romano V, Belviso I, Carfora A, Montagnani S, Arcucci A. Metabolic reprogramming of cancer associated fibroblasts: the slavery of stromal fibroblasts. Biomed Res Int. 2018;2018:6075403.PubMedPubMedCentralCrossRef
168.
Hu JW, Sun P, Zhang DX, Xiong WJ, Mi J. Hexokinase 2 regulates G1/S checkpoint through CDK2 in cancer-associated fibroblasts. Cell Signal. 2014;26(10):2210–6.PubMedCrossRef
169.
Papandreou I, Cairns RA, Fontana L, Lim AL, Denko NC. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab. 2006;3(3):187–97.PubMedCrossRef
170.
Kim JW, Tchernyshyov I, Semenza GL, Dang CV. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006;3(3):177–85.PubMedCrossRef
171.
Meng W, Xia Q, Wu L, Chen S, He X, Zhang L, Gao Q, Zhou H. Downregulation of TGF-beta receptor types II and III in oral squamous cell carcinoma and oral carcinoma-associated fibroblasts. BMC Cancer. 2011;11:88.PubMedPubMedCentralCrossRef
172.
Martinez-Outschoorn UE, Lin Z, Trimmer C, Flomenberg N, Wang C, Pavlides S, Pestell RG, Howell A, Sotgia F, Lisanti MP. Cancer cells metabolically “fertilize” the tumor microenvironment with hydrogen peroxide, driving the Warburg effect: implications for PET imaging of human tumors. Cell Cycle. 2011;10(15):2504–20 (Georgetown, Tex).PubMedPubMedCentralCrossRef
173.
Martinez-Outschoorn UE, Balliet RM, Rivadeneira DB, Chiavarina B, Pavlides S, Wang C, Whitaker-Menezes D, Daumer KM, Lin Z, Witkiewicz AK, et al. Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: a new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells. Cell Cycle. 2010;9(16):3256–76 (Georgetown, Tex).PubMedPubMedCentralCrossRef
174.
Shimura T, Sasatani M, Kawai H, Kamiya K, Kobayashi J, Komatsu K, Kunugita N. Radiation-induced myofibroblasts promote tumor growth via mitochondrial ROS-activated TGFβ signaling. Mol Cancer Res: MCR. 2018;16(11):1676–86.PubMedCrossRef
175.
Cruz-Bermúdez A, Laza-Briviesca R, Vicente-Blanco RJ, García-Grande A, Coronado MJ, Laine-Menéndez S, Alfaro C, Sanchez JC, Franco F, Calvo V, et al. Cancer-associated fibroblasts modify lung cancer metabolism involving ROS and TGF-β signaling. Free Radical Biol Med. 2019;130:163–73.CrossRef
176.
Ayala G, Morello M, Frolov A, You S, Li R, Rosati F, Bartolucci G, Danza G, Adam RM, Thompson TC, et al. Loss of caveolin-1 in prostate cancer stroma correlates with reduced relapse-free survival and is functionally relevant to tumour progression. J Pathol. 2013;231(1):77–87.PubMedPubMedCentralCrossRef
177.
Zhu Z, Achreja A, Meurs N, Animasahun O, Owen S, Mittal A, Parikh P, Lo TW, Franco-Barraza J, Shi J, et al. Tumour-reprogrammed stromal BCAT1 fuels branched-chain ketoacid dependency in stromal-rich PDAC tumours. Nat Metab. 2020;2(8):775–92.PubMedPubMedCentralCrossRef
178.
179.
Kohlgruber AC, LaMarche NM, Lynch L. Adipose tissue at the nexus of systemic and cellular immunometabolism. Semin Immunol. 2016;28(5):431–40.PubMedCrossRef
180.
Myers JA, Miller JS. Exploring the NK cell platform for cancer immunotherapy. Nat Rev Clin Oncol. 2021;18(2):85–100.PubMedCrossRef
181.
Terrén I, Orrantia A, Vitallé J, Astarloa-Pando G, Zenarruzabeitia O, Borrego F. Modulating NK cell metabolism for cancer immunotherapy. Semin Hematol. 2020;57(4):213–24.PubMedCrossRef
182.
Salzberger W, Martrus G, Bachmann K, Goebels H, Heß L, Koch M, Langeneckert A, Lunemann S, Oldhafer KJ, Pfeifer C, et al. Tissue-resident NK cells differ in their expression profile of the nutrient transporters Glut1, CD98 and CD71. PLoS ONE. 2018;13(7):e0201170.PubMedPubMedCentralCrossRef
183.
Keating SE, Zaiatz-Bittencourt V, Loftus RM, Keane C, Brennan K, Finlay DK, Gardiner CM. Metabolic reprogramming supports IFN-γ production by CD56bright NK cells. J Immunol (Baltimore, Md : 1950). 2016;196(6):2552–60.CrossRef
184.
Cong J, Wang X, Zheng X, Wang D, Fu B, Sun R, Tian Z, Wei H. Dysfunction of natural killer cells by FBP1-induced inhibition of glycolysis during lung cancer progression. Cell Metab. 2018;28(2):243-255.e245.PubMedCrossRef
185.
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.PubMedPubMedCentralCrossRef
186.
Loftus RM, Assmann N, Kedia-Mehta N, O’Brien KL, Garcia A, Gillespie C, Hukelmann JL, Oefner PJ, Lamond AI, Gardiner CM, et al. Amino acid-dependent cMyc expression is essential for NK cell metabolic and functional responses in mice. Nat Commun. 2018;9(1):2341.PubMedPubMedCentralCrossRef
187.
188.
Wu FL, Nolan K, Strait AA, Bian L, Nguyen KA, Wang JH, Jimeno A, Zhou HM, Young CD, Wang XJ. Macrophages promote growth of squamous cancer independent of T cells. J Dent Res. 2019;98(8):896–903.PubMedPubMedCentralCrossRef
189.
Liu D, Chang C, Lu N, Wang X, Lu Q, Ren X, Ren P, Zhao D, Wang L, Zhu Y, et al. Comprehensive proteomics analysis reveals metabolic reprogramming of tumor-associated macrophages stimulated by the tumor microenvironment. J Proteome Res. 2017;16(1):288–97.PubMedCrossRef
190.
Arts RJW, Plantinga TS, Tuit S, Ulas T, Heinhuis B, Tesselaar M, Sloot Y, Adema GJ, Joosten LAB, Smit JWA, et al. Transcriptional and metabolic reprogramming induce an inflammatory phenotype in non-medullary thyroid carcinoma-induced macrophages. Oncoimmunology. 2016;5(12):e1229725.PubMedPubMedCentralCrossRef
191.
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. Can Res. 2020;80(7):1438–50.CrossRef
192.
Jha AK, Huang SC, Sergushichev A, Lampropoulou V, Ivanova Y, Loginicheva E, Chmielewski K, Stewart KM, Ashall J, Everts B, et al. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity. 2015;42(3):419–30.PubMedCrossRef
193.
Masucci MT, Minopoli M, Del Vecchio S, Carriero MV. The emerging role of neutrophil extracellular traps (NETs) in tumor progression and metastasis. Front Immunol. 2020;11:1749.PubMedPubMedCentralCrossRef
194.
Mollinedo F. Neutrophil degranulation, plasticity, and cancer metastasis. Trends Immunol. 2019;40(3):228–42.PubMedCrossRef
195.
Jaillon S, Ponzetta A, Di Mitri D, Santoni A, Bonecchi R, Mantovani A. Neutrophil diversity and plasticity in tumour progression and therapy. Nat Rev Cancer. 2020;20(9):485–503.PubMedCrossRef
196.
Jun HS, Weinstein DA, Lee YM, Mansfield BC, Chou JY. Molecular mechanisms of neutrophil dysfunction in glycogen storage disease type Ib. Blood. 2014;123(18):2843–53.PubMedPubMedCentralCrossRef
197.
Ancey PB, Contat C, Boivin G, Sabatino S, Pascual J, Zangger N, Perentes JY, Peters S, Abel ED, Kirsch DG, et al. GLUT1 expression in tumor-associated neutrophils promotes lung cancer growth and resistance to radiotherapy. Can Res. 2021;81(9):2345–57.CrossRef
198.
Rice CM, Davies LC, Subleski JJ, Maio N, Gonzalez-Cotto M, Andrews C, Patel NL, Palmieri EM, Weiss JM, Lee JM, et al. Tumour-elicited neutrophils engage mitochondrial metabolism to circumvent nutrient limitations and maintain immune suppression. Nat Commun. 2018;9(1):5099.PubMedPubMedCentralCrossRef
199.
Veglia F, Sanseviero E, Gabrilovich DI. Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity. Nat Rev Immunol. 2021;21(8):485–98.PubMedPubMedCentralCrossRef
200.
201.
202.
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.PubMedPubMedCentralCrossRef
203.
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.PubMedPubMedCentralCrossRef
204.
Balan S, Arnold-Schrauf C, Abbas A, Couespel N, Savoret J, Imperatore F, Villani AC, Vu Manh TP, Bhardwaj N, Dalod M. Large-scale human dendritic cell differentiation revealing notch-dependent lineage bifurcation and heterogeneity. Cell Rep. 2018;24(7):1902-1915.e1906.PubMedPubMedCentralCrossRef
205.
Li Y, Wan YY, Zhu B. Immune cell metabolism in tumor microenvironment. Adv Exp Med Biol. 2017;1011:163–96.PubMedCrossRef
206.
Gardner JK, Mamotte CDS, Patel P, Yeoh TL, Jackaman C, Nelson DJ. Mesothelioma tumor cells modulate dendritic cell lipid content, phenotype and function. PLoS ONE. 2015;10(4):e0123563.PubMedPubMedCentralCrossRef
207.
Peng X, He Y, Huang J, Tao Y, Liu S. Metabolism of dendritic cells in tumor microenvironment: for immunotherapy. Front Immunol. 2021;12:613492–613492.PubMedPubMedCentralCrossRef
208.
Kouidhi S, Noman MZ, Kieda C, Elgaaied AB, Chouaib S. Intrinsic and tumor microenvironment-induced metabolism adaptations of T cells and impact on their differentiation and function. Front Immunol. 2016;7:114–114.PubMedPubMedCentralCrossRef
209.
Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF, Sullivan SA, Nichols AG, Rathmell JC. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol (Baltimore, Md: 1950). 2011;186(6):3299–303.CrossRef
210.
Sukumar M, Liu J, Ji Y, Subramanian M, Crompton JG, Yu Z, Roychoudhuri R, Palmer DC, Muranski P, Karoly ED, et al. Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function. J Clin Investig. 2013;123(10):4479–88.PubMedPubMedCentralCrossRef
211.
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.PubMedPubMedCentralCrossRef
212.
Molon B, Ugel S, Del Pozzo F, Soldani C, Zilio S, Avella D, De Palma A, Mauri P, Monegal A, Rescigno M, et al. Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells. J Exp Med. 2011;208(10):1949–62.PubMedPubMedCentralCrossRef
213.
Munn DH, Sharma MD, Baban B, Harding HP, Zhang Y, Ron D, Mellor AL. GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. Immunity. 2005;22(5):633–42.PubMedCrossRef
214.
Kim J-w. Gao P, Liu Y-C, Semenza GL, Dang CV: Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1. Mol Cell Biol. 2007;27(21):7381–93.PubMedPubMedCentralCrossRef
215.
Osthus RC, Shim H, Kim S, Li Q, Reddy R, Mukherjee M, Xu Y, Wonsey D, Lee LA, Dang CV. Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc. J Biol Chem. 2000;275(29):21797–800.PubMedCrossRef
216.
Scarpulla RC. Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev. 2008;88(2):611–38.PubMedCrossRef
217.
Caro-Maldonado A, Wang R, Nichols AG, Kuraoka M, Milasta S, Sun LD, Gavin AL, Abel ED, Kelsoe G, Green DR, et al. Metabolic reprogramming is required for antibody production that is suppressed in anergic but exaggerated in chronically BAFF-exposed B cells. J Immunol (Baltimore, Md: 1950). 2014;192(8):3626–36.CrossRef
218.
Derynck R, Turley SJ, Akhurst RJ. TGFβ biology in cancer progression and immunotherapy. Nat Rev Clin Oncol. 2021;18(1):9–34.PubMedCrossRef
219.
Slattery K, Woods E, Zaiatz-Bittencourt V, Marks S, Chew S, Conroy M, Goggin C, MacEochagain C, Kennedy J, Lucas S, et al. TGFβ drives NK cell metabolic dysfunction in human metastatic breast cancer. J Immunother Cancer. 2021;9(2):e002044.PubMedPubMedCentralCrossRef
220.
Zaiatz-Bittencourt V, Finlay DK, Gardiner CM. Canonical TGF-β signaling pathway represses human NK cell metabolism. J Immunol (Baltimore, Md : 1950). 2018;200(12):3934–41.CrossRef
221.
Park JE, Dutta B, Tse SW, Gupta N, Tan CF, Low JK, Yeoh KW, Kon OL, Tam JP, Sze SK. Hypoxia-induced tumor exosomes promote M2-like macrophage polarization of infiltrating myeloid cells and microRNA-mediated metabolic shift. Oncogene. 2019;38(26):5158–73.PubMedCrossRef
222.
223.
Arlauckas SP, Garren SB, Garris CS, Kohler RH, Oh J, Pittet MJ, Weissleder R. Arg1 expression defines immunosuppressive subsets of tumor-associated macrophages. Theranostics. 2018;8(21):5842–54.PubMedPubMedCentralCrossRef
224.
Gómez V, Eykyn TR, Mustapha R, Flores-Borja F, Male V, Barber PR, Patsialou A, Green R, Panagaki F, Li CW, et al. Breast cancer-associated macrophages promote tumorigenesis by suppressing succinate dehydrogenase in tumor cells. Sci Signal. 2020;13(652):eaax4585.PubMedCrossRef
225.
Rotondo R, Barisione G, Mastracci L, Grossi F, Orengo AM, Costa R, Truini M, Fabbi M, Ferrini S, Barbieri O. IL-8 induces exocytosis of arginase 1 by neutrophil polymorphonuclears in nonsmall cell lung cancer. Int J Cancer. 2009;125(4):887–93.PubMedCrossRef
226.
Pang Y, Gara SK, Achyut BR, Li Z, Yan HH, Day CP, Weiss JM, Trinchieri G, Morris JC, Yang L. TGF-β signaling in myeloid cells is required for tumor metastasis. Cancer Discov. 2013;3(8):936–51.PubMedPubMedCentralCrossRef
227.
Angioni R, Liboni C, Herkenne S, Sánchez-Rodríguez R, Borile G, Marcuzzi E, Calì B, Muraca M, Viola A. CD73(+) extracellular vesicles inhibit angiogenesis through adenosine A(2B) receptor signalling. J Extracell Vesicles. 2020;9(1):1757900.PubMedPubMedCentralCrossRef
228.
Groth C, Hu X, Weber R, Fleming V, Altevogt P, Utikal J, Umansky V. Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression. Br J Cancer. 2019;120(1):16–25.PubMedCrossRef
229.
Li J, Wang L, Chen X, Li L, Li Y, Ping Y, Huang L, Yue D, Zhang Z, Wang F, et al. CD39/CD73 upregulation on myeloid-derived suppressor cells via TGF-β-mTOR-HIF-1 signaling in patients with non-small cell lung cancer. Oncoimmunology. 2017;6(6):e1320011.PubMedPubMedCentralCrossRef
230.
Priyadharshini B, Loschi M, Newton RH, Zhang J-W, Finn KK, Gerriets VA, Huynh A, Rathmell JC, Blazar BR, Turka LA. Cutting edge: TGF-β and phosphatidylinositol 3-kinase signals modulate distinct metabolism of regulatory T cell subsets. J Immunol (Baltimore, Md : 1950). 2018;201(8):2215–9.CrossRef
231.
Ho PC, Bihuniak JD, Macintyre AN, Staron M, Liu X, Amezquita R, Tsui YC, Cui G, Micevic G, Perales JC, et al. Phosphoenolpyruvate Is a Metabolic checkpoint of anti-tumor T cell responses. Cell. 2015;162(6):1217–28.PubMedPubMedCentralCrossRef
232.
Cham CM, Driessens G, O’Keefe JP, Gajewski TF. Glucose deprivation inhibits multiple key gene expression events and effector functions in CD8+ T cells. Eur J Immunol. 2008;38(9):2438–50.PubMedPubMedCentralCrossRef
233.
Renner K, Bruss C, Schnell A, Koehl G, Becker HM, Fante M, Menevse AN, Kauer N, Blazquez R, Hacker L, et al. Restricting glycolysis preserves T cell effector functions and augments checkpoint therapy. Cell Rep. 2019;29(1):135-150.e139.PubMedCrossRef
234.
Cascone T, McKenzie JA, Mbofung RM, Punt S, Wang Z, Xu C, Williams LJ, Wang Z, Bristow CA, Carugo A, et al. Increased tumor glycolysis characterizes immune resistance to adoptive T cell therapy. Cell Metab. 2018;27(5):977-987.e974.PubMedPubMedCentralCrossRef
235.
Dimeloe S, Gubser P, Loeliger J, Frick C, Develioglu L, Fischer M, Marquardsen F, Bantug GR, Thommen D, Lecoultre Y, et al. Tumor-derived TGF-β inhibits mitochondrial respiration to suppress IFN-γ production by human CD4(+) T cells. Sci Signal. 2019;12(599):eaav3334.PubMedCrossRef
236.
Gasparics Á, Rosivall L, Krizbai IA, Sebe A. When the endothelium scores an own goal: endothelial cells actively augment metastatic extravasation through endothelial-mesenchymal transition. Am J Physiol Heart Circ Physiol. 2016;310(9):H1055-1063.PubMedCrossRef
237.
Cantelmo AR, Conradi L-C, Brajic A, Goveia J, Kalucka J, Pircher A, Chaturvedi P, Hol J, Thienpont B, Teuwen L-A, et al. Inhibition of the glycolytic activator PFKFB3 in endothelium induces tumor vessel normalization, impairs metastasis, and improves chemotherapy. Cancer Cell. 2016;30(6):968–85.PubMedPubMedCentralCrossRef
238.
Zhang L, Li S, Li L, Chen Z, Yang Y. COX-2 inhibition in the endothelium induces glucose metabolism normalization and impairs tumor progression. Mol Med Rep. 2018;17(2):2937–44.PubMed
239.
Hinshaw DB, Burger JM. Protective effect of glutamine on endothelial cell ATP in oxidant injury. J Surg Res. 1990;49(3):222–7.PubMedCrossRef
240.
Ning J, Zhao Y, Ye Y, Yu J. Opposing roles and potential antagonistic mechanism between TGF-β and BMP pathways: implications for cancer progression. EBioMedicine. 2019;41:702–10.PubMedPubMedCentralCrossRef
241.
Howell ED, Yzaguirre AD, Gao P, Lis R, He B, Lakadamyali M, Rafii S, Tan K, Speck NA. Efficient hemogenic endothelial cell specification by RUNX1 is dependent on baseline chromatin accessibility of RUNX1-regulated TGFβ target genes. Genes Dev. 2021;35(21–22):1475–89.PubMedPubMedCentralCrossRef
242.
Xiong J, Kawagishi H, Yan Y, Liu J, Wells QS, Edmunds LR, Fergusson MM, Yu ZX, Rovira II, Brittain EL, et al. A metabolic basis for endothelial-to-mesenchymal transition. Mol Cell. 2018;69(4):689-698.e687.PubMedPubMedCentralCrossRef
243.
244.
Armulik A, Genové G, Betsholtz C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell. 2011;21(2):193–215.PubMedCrossRef
245.
Zonneville J, Safina A, Truskinovsky AM, Arteaga CL, Bakin AV. TGF-β signaling promotes tumor vasculature by enhancing the pericyte-endothelium association. BMC Cancer. 2018;18(1):670–670.PubMedPubMedCentralCrossRef
246.
Yeh WL, Lin CJ, Fu WM. Enhancement of glucose transporter expression of brain endothelial cells by vascular endothelial growth factor derived from glioma exposed to hypoxia. Mol Pharmacol. 2008;73(1):170–7.PubMedCrossRef
247.
Wenes M, Shang M, Di Matteo M, Goveia J, Martín-Pérez R, Serneels J, Prenen H, Ghesquière B, Carmeliet P, Mazzone M. Macrophage metabolism controls tumor blood vessel morphogenesis and metastasis. Cell Metab. 2016;24(5):701–15.PubMedCrossRef
248.
Guo Y, Deng Y, Li X, Ning Y, Lin X, Guo S, Chen M, Han M. Glutaminolysis was induced by TGF-β1 through PP2Ac regulated Raf-MEK-ERK signaling in endothelial cells. PLoS ONE. 2016;11(9):e0162658.PubMedPubMedCentralCrossRef
249.
Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, Romero IL, Carey MS, Mills GB, Hotamisligil GS, et al. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med. 2011;17(11):1498–503.PubMedPubMedCentralCrossRef
250.
Clement E, Lazar I, Attané C, Carrié L, Dauvillier S, Ducoux-Petit M, Esteve D, Menneteau T, Moutahir M, Le Gonidec S, et al. Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells. EMBO J. 2020;39(3):e102525.PubMedPubMedCentralCrossRef
251.
Seo J, Kim KS, Park JW, Cho JY, Chang H, Fukuda J, Hong KY, Chun YS. Metastasis-on-a-chip reveals adipocyte-derived lipids trigger cancer cell migration via HIF-1α activation in cancer cells. Biomaterials. 2021;269:120622.PubMedCrossRef
252.
Karsten E, Breen E, McCracken SA, Clarke S, Herbert BR. Red blood cells exposed to cancer cells in culture have altered cytokine profiles and immune function. Sci Rep. 2020;10(1):7727.PubMedPubMedCentralCrossRef
253.
Hercbergs A, Brok-Simoni F, Holtzman F, Bar-Am J, Leith JT, Brenner HJ. Erythrocyte glutathione and tumour response to chemotherapy. Lancet. 1992;339(8801):1074–6 (London, England).PubMedCrossRef
254.
Sharma A, Smyrk TC, Levy MJ, Topazian MA, Chari ST. Fasting blood glucose levels provide estimate of duration and progression of pancreatic cancer Before diagnosis. Gastroenterology. 2018;155(2):490-500.e492.PubMedCrossRef
255.
Lee J-H, Mellado-Gil JM, Bahn YJ, Pathy SM, Zhang YE, Rane SG. Protection from β-cell apoptosis by inhibition of TGF-β/Smad3 signaling. Cell Death Dis. 2020;11(3):184.PubMedPubMedCentralCrossRef
256.
257.
Yadav H, Devalaraja S, Chung ST, Rane SG. TGF-β1/Smad3 pathway targets PP2A-AMPK-FoxO1 signaling to regulate hepatic gluconeogenesis. J Biol Chem. 2017;292(8):3420–32.PubMedPubMedCentralCrossRef
258.
Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12(5):489–95.PubMedCrossRef
259.
Pin F, Barreto R, Couch ME, Bonetto A, O’Connell TM. Cachexia induced by cancer and chemotherapy yield distinct perturbations to energy metabolism. J Cachexia Sarcopenia Muscle. 2019;10(1):140–54.PubMedPubMedCentralCrossRef
260.
Penna F, Costamagna D, Pin F, Camperi A, Fanzani A, Chiarpotto EM, Cavallini G, Bonelli G, Baccino FM, Costelli P. Autophagic degradation contributes to muscle wasting in cancer cachexia. Am J Pathol. 2013;182(4):1367–78.PubMedCrossRef
261.
Penna F, Ballarò R, Martinez-Cristobal P, Sala D, Sebastian D, Busquets S, Muscaritoli M, Argilés JM, Costelli P, Zorzano A. Autophagy exacerbates muscle wasting in cancer cachexia and impairs mitochondrial function. J Mol Biol. 2019;431(15):2674–86.PubMedCrossRef
262.
Yang X, Xue P, Liu X, Xu X, Chen Z. HMGB1/autophagy pathway mediates the atrophic effect of TGF-β1 in denervated skeletal muscle. Cell Commun Signal. 2018;16(1):97.PubMedPubMedCentralCrossRef
263.
Greco SH, Tomkötter L, Vahle AK, Rokosh R, Avanzi A, Mahmood SK, Deutsch M, Alothman S, Alqunaibit D, Ochi A, et al. TGF-β blockade reduces mortality and metabolic changes in a validated murine model of pancreatic cancer cachexia. PLoS ONE. 2015;10(7):e0132786.PubMedPubMedCentralCrossRef
264.
Lacouture ME, Morris JC, Lawrence DP, Tan AR, Olencki TE, Shapiro GI, Dezube BJ, Berzofsky JA, Hsu FJ, Guitart J. Cutaneous keratoacanthomas/squamous cell carcinomas associated with neutralization of transforming growth factor β by the monoclonal antibody fresolimumab (GC1008). Cancer Immunol Immunother. 2015;64(4):437–46.PubMedPubMedCentralCrossRef
265.
Lacouture ME, Morris JC, Lawrence DP, Tan AR, Olencki TE, Shapiro GI, Dezube BJ, Berzofsky JA, Hsu FJ, Guitart J. Cutaneous keratoacanthomas/squamous cell carcinomas associated with neutralization of transforming growth factor β by the monoclonal antibody fresolimumab (GC1008). Cancer Immunol Immunother: CII. 2015;64(4):437–46.PubMedCrossRef
266.
Osumi H, Horiguchi H, Kadomatsu T, Tashiro K, Morinaga J, Takahashi T, Ikeda K, Ito T, Suzuki M, Endo M, et al. Tumor cell-derived angiopoietin-like protein 2 establishes a preference for glycolytic metabolism in lung cancer cells. Cancer Sci. 2020;111(4):1241–53.PubMedPubMedCentralCrossRef
267.
Cheng KY, Hao M. Mammalian target of rapamycin (mTOR) regulates transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition via decreased pyruvate kinase M2 (PKM2) expression in cervical cancer cells. Med Sci Monit. 2017;23:2017–28.PubMedPubMedCentralCrossRef
268.
Haidar M, Metheni M, Batteux F, Langsley G. TGF-β2, catalase activity, H(2)O(2) output and metastatic potential of diverse types of tumour. Free Radical Biol Med. 2019;134:282–7.CrossRef
269.
Zhao Y, Xia S, Cao C, Du X. Effect of TGF-β1 on apoptosis of colon cancer cells via the ERK signaling pathway. J BUON. 2019;24(2):449–55.PubMed
270.
Soukupova J, Malfettone A, Bertran E, Hernández-Alvarez MI, Peñuelas-Haro I, Dituri F, Giannelli G, Zorzano A, Fabregat I. Epithelial-mesenchymal transition (EMT) induced by TGF-β in hepatocellular carcinoma cells reprograms lipid metabolism. Int J Mol Sci. 2021;22(11):5543.PubMedPubMedCentralCrossRef
271.
Flaig TW, Glode M, Gustafson D, van Bokhoven A, Tao Y, Wilson S, Su LJ, Li Y, Harrison G, Agarwal R, et al. A study of high-dose oral silybin-phytosome followed by prostatectomy in patients with localized prostate cancer. Prostate. 2010;70(8):848–55.PubMedCrossRef
272.
Guo Z, Cheng Z, Wang J, Liu W, Peng H, Wang Y, Rao AVS, Li RJ, Ying X, Korangath P, et al. Discovery of a potent GLUT inhibitor from a library of rapafucins by using 3D microarrays. Angew Chem Int Ed Engl. 2019;58(48):17158–62.PubMedPubMedCentralCrossRef
273.
Lord SR, Collins JM, Cheng WC, Haider S, Wigfield S, Gaude E, Fielding BA, Pinnick KE, Harjes U, Segaran A, et al. Transcriptomic analysis of human primary breast cancer identifies fatty acid oxidation as a target for metformin. Br J Cancer. 2020;122(2):258–65.PubMedCrossRef
274.
Stein M, Lin H, Jeyamohan C, Dvorzhinski D, Gounder M, Bray K, Eddy S, Goodin S, White E, Dipaola RS. Targeting tumor metabolism with 2-deoxyglucose in patients with castrate-resistant prostate cancer and advanced malignancies. Prostate. 2010;70(13):1388–94.PubMedPubMedCentralCrossRef
275.
Sun X, Sun G, Huang Y, Hao Y, Tang X, Zhang N, Zhao L, Zhong R, Peng Y. 3-Bromopyruvate regulates the status of glycolysis and BCNU sensitivity in human hepatocellular carcinoma cells. Biochem Pharmacol. 2020;177:113988.PubMedCrossRef
276.
Yang Q, Miyagawa M, Liu X, Zhu B, Munemasa S, Nakamura T, Murata Y, Nakamura Y. Methyl-β-cyclodextrin potentiates the BITC-induced anti-cancer effect through modulation of the Akt phosphorylation in human colorectal cancer cells. Biosci Biotechnol Biochem. 2018;82(12):2158–67.PubMedCrossRef
277.
McNeillis R, Greystoke A, Walton J, Bacon C, Keun H, Siskos A, Petrides G, Leech N, Jenkinson F, Bowron A, et al. A case of malignant hyperlactaemic acidosis appearing upon treatment with the mono-carboxylase transporter 1 inhibitor AZD3965. Br J Cancer. 2020;122(8):1141–5.PubMedPubMedCentralCrossRef
278.
Chu QS, Sangha R, Spratlin J, Vos LJ, Mackey JR, McEwan AJ, Venner P, Michelakis ED. A phase I open-labeled, single-arm, dose-escalation, study of dichloroacetate (DCA) in patients with advanced solid tumors. Invest New Drugs. 2015;33(3):603–10.PubMedCrossRef
279.
Dai Y, Xiong X, Huang G, Liu J, Sheng S, Wang H, Qin W. Dichloroacetate enhances adriamycin-induced hepatoma cell toxicity in vitro and in vivo by increasing reactive oxygen species levels. PLoS ONE. 2014;9(4):e92962.PubMedPubMedCentralCrossRef
280.
Anwar S, Mohammad T, Shamsi A, Queen A, Parveen S, Luqman S, Hasan GM, Alamry KA, Azum N, Asiri AM, et al. Discovery of hordenine as a potential inhibitor of pyruvate dehydrogenase kinase 3: implication in lung cancer therapy. Biomedicines. 2020;8(5):119.PubMedCentralCrossRef
281.
Mellinghoff IK, Ellingson BM, Touat M, Maher E, De La Fuente MI, Holdhoff M, Cote GM, Burris H, Janku F, Young RJ, et al. Ivosidenib in isocitrate dehydrogenase 1-mutated advanced glioma. J Clin Oncol. 2020;38(29):3398–406.PubMedPubMedCentralCrossRef
282.
Abou-Alfa GK, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, Cleary JM, Catenacci DV, Borad MJ, Bridgewater J, et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(6):796–807.PubMedPubMedCentralCrossRef
283.
Tong Z, Atsriku C, Yerramilli U, Wang X, Li Y, Reyes J, Fan B, Yang H, Hoffmann M, Surapaneni S. Absorption, distribution, metabolism and excretion of an isocitrate dehydrogenase-2 inhibitor enasidenib in rats and humans. Xenobiotica. 2019;49(2):200–10.PubMedCrossRef
284.
Stein EM, DiNardo CD, Pollyea DA, Fathi AT, Roboz GJ, Altman JK, Stone RM, DeAngelo DJ, Levine RL, Flinn IW, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017;130(6):722–31.PubMedPubMedCentralCrossRef
285.
Chen J, Yang J, Cao P. The evolving landscape in the development of isocitrate dehydrogenase mutant inhibitors. Mini Rev Med Chem. 2016;16(16):1344–58.PubMedCrossRef
286.
Caravella JA, Lin J, Diebold RB, Campbell AM, Ericsson A, Gustafson G, Wang Z, Castro J, Clarke A, Gotur D, et al. Structure-based design and identification of FT-2102 (Olutasidenib), a potent mutant-selective IDH1 inhibitor. J Med Chem. 2020;63(4):1612–23.PubMedCrossRef
287.
Konteatis Z, Artin E, Nicolay B, Straley K, Padyana AK, Jin L, Chen Y, Narayaraswamy R, Tong S, Wang F, et al. Vorasidenib (AG-881): a first-in-class, brain-penetrant dual inhibitor of mutant IDH1 and 2 for treatment of glioma. ACS Med Chem Lett. 2020;11(2):101–7.PubMedPubMedCentralCrossRef
288.
Lee WJ, Chen WK, Wang CJ, Lin WL, Tseng TH. Apigenin inhibits HGF-promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and beta 4 integrin function in MDA-MB-231 breast cancer cells. Toxicol Appl Pharmacol. 2008;226(2):178–91.PubMedCrossRef
289.
Shukla S, Gupta S. Apigenin-induced cell cycle arrest is mediated by modulation of MAPK, PI3K-Akt, and loss of cyclin D1 associated retinoblastoma dephosphorylation in human prostate cancer cells. Cell Cycle. 2007;6(9):1102–14 (Georgetown, Tex).PubMedCrossRef
290.
Fang J, Zhou Q, Liu LZ, Xia C, Hu X, Shi X, Jiang BH. Apigenin inhibits tumor angiogenesis through decreasing HIF-1alpha and VEGF expression. Carcinogenesis. 2007;28(4):858–64.PubMedCrossRef
291.
Fang J, Xia C, Cao Z, Zheng JZ, Reed E, Jiang BH. Apigenin inhibits VEGF and HIF-1 expression via PI3K/AKT/p70S6K1 and HDM2/p53 pathways. FASEB J. 2005;19(3):342–53.PubMedCrossRef
292.
Tang W, Zhao G. Small molecules targeting HIF-1α pathway for cancer therapy in recent years. Bioorg Med Chem. 2020;28(2):115235.PubMedCrossRef
293.
Mita MM, Rowinsky EK, Forero L, Eckhart SG, Izbicka E, Weiss GR, Beeram M, Mita AC, de Bono JS, Tolcher AW, et al. A phase II, pharmacokinetic, and biologic study of semaxanib and thalidomide in patients with metastatic melanoma. Cancer Chemother Pharmacol. 2007;59(2):165–74.PubMedCrossRef
294.
Ricker JL, Chen Z, Yang XP, Pribluda VS, Swartz GM, Van Waes C. 2-methoxyestradiol inhibits hypoxia-inducible factor 1alpha, tumor growth, and angiogenesis and augments paclitaxel efficacy in head and neck squamous cell carcinoma. Clin Cancer Res. 2004;10(24):8665–73.PubMedCrossRef
295.
Mooberry SL. Mechanism of action of 2-methoxyestradiol: new developments. Drug Resist Updat. 2003;6(6):355–61.PubMedCrossRef
296.
Sibonga JD, Lotinun S, Evans GL, Pribluda VS, Green SJ, Turner RT. Dose-response effects of 2-methoxyestradiol on estrogen target tissues in the ovariectomized rat. Endocrinology. 2003;144(3):785–92.PubMedCrossRef
297.
Zhu Y, Zang Y, Zhao F, Li Z, Zhang J, Fang L, Li M, Xing L, Xu Z, Yu J. Inhibition of HIF-1α by PX-478 suppresses tumor growth of esophageal squamous cell cancer in vitro and in vivo. Am J Cancer Res. 2017;7(5):1198–212.PubMedPubMedCentral
298.
Koh MY, Spivak-Kroizman T, Venturini S, Welsh S, Williams RR, Kirkpatrick DL, Powis G. Molecular mechanisms for the activity of PX-478, an antitumor inhibitor of the hypoxia-inducible factor-1alpha. Mol Cancer Ther. 2008;7(1):90–100.PubMedCrossRef
299.
Lee K, Kim HM. A novel approach to cancer therapy using PX-478 as a HIF-1α inhibitor. Arch Pharm Res. 2011;34(10):1583–5.PubMedCrossRef
300.
Li YL, Rao MJ, Zhang NY, Wu LW, Lin NM, Zhang C. BAY 87–2243 sensitizes hepatocellular carcinoma Hep3B cells to histone deacetylase inhibitors treatment via GSK-3β activation. Exp Ther Med. 2019;17(6):4547–53.PubMedPubMedCentral
301.
Schöckel L, Glasauer A, Basit F, Bitschar K, Truong H, Erdmann G, Algire C, Hägebarth A, Willems PH, Kopitz C, et al. Targeting mitochondrial complex I using BAY 87–2243 reduces melanoma tumor growth. Cancer Metab. 2015;3:11.PubMedPubMedCentralCrossRef
302.
Ellinghaus P, Heisler I, Unterschemmann K, Haerter M, Beck H, Greschat S, Ehrmann A, Summer H, Flamme I, Oehme F, et al. BAY 87–2243, a highly potent and selective inhibitor of hypoxia-induced gene activation has antitumor activities by inhibition of mitochondrial complex I. Cancer Med. 2013;2(5):611–24.PubMedPubMedCentralCrossRef
303.
Oudard S, Carpentier A, Banu E, Fauchon F, Celerier D, Poupon MF, Dutrillaux B, Andrieu JM, Delattre JY. Phase II study of lonidamine and diazepam in the treatment of recurrent glioblastoma multiforme. J Neurooncol. 2003;63(1):81–6.PubMedCrossRef
304.
Nath K, Guo L, Nancolas B, Nelson DS, Shestov AA, Lee SC, Roman J, Zhou R, Leeper DB, Halestrap AP, et al. Mechanism of antineoplastic activity of lonidamine. Biochem Biophys Acta. 2016;1866(2):151–62.PubMed
305.
Rutkowski K, Sowa P, Rutkowska-Talipska J, Kuryliszyn-Moskal A, Rutkowski R. Dehydroepiandrosterone (DHEA): hypes and hopes. Drugs. 2014;74(11):1195–207.PubMedCrossRef
306.
Mele L, la Noce M, Paino F, Regad T, Wagner S, Liccardo D, Papaccio G, Lombardi A, Caraglia M, Tirino V, et al. Glucose-6-phosphate dehydrogenase blockade potentiates tyrosine kinase inhibitor effect on breast cancer cells through autophagy perturbation. J Exp Clin Cancer Res: CR. 2019;38(1):160.PubMedPubMedCentralCrossRef
307.
O’Donovan TR, Rajendran S, O’Reilly S, O’Sullivan GC, McKenna SL. Lithium modulates autophagy in esophageal and colorectal cancer cells and enhances the efficacy of therapeutic agents in vitro and in vivo. PLoS ONE. 2015;10(8):e0134676.PubMedPubMedCentralCrossRef
308.
Huang K, Liang Q, Zhou Y, Jiang LL, Gu WM, Luo MY, Tang YB, Wang Y, Lu W, Huang M, et al. A novel allosteric inhibitor of phosphoglycerate mutase 1 suppresses growth and metastasis of non-small-cell lung cancer. Cell Metab. 2019;30(6):1107-1119.e1108.PubMedCrossRef
309.
Hitosugi T, Zhou L, Elf S, Fan J, Kang HB, Seo JH, Shan C, Dai Q, Zhang L, Xie J, et al. Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth. Cancer Cell. 2012;22(5):585–600.
310.
Cotte AK, Aires V, Fredon M, Limagne E, Derangère 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.PubMedPubMedCentralCrossRef
311.
Yen MC, Kan JY, Hsieh CJ, Kuo PL, Hou MF, Hsu YL. Association of long-chain acyl-coenzyme a synthetase 5 expression in human breast cancer by estrogen receptor status and its clinical significance. Oncol Rep. 2017;37(6):3253–60.PubMedCrossRef
312.
Ayyagari VN, Wang X, Diaz-Sylvester PL, Groesch K, Brard L. Assessment of acyl-CoA cholesterol acyltransferase (ACAT-1) role in ovarian cancer progression-an in vitro study. PLoS ONE. 2020;15(1):e0228024.PubMedPubMedCentralCrossRef
313.
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.PubMedPubMedCentralCrossRef
314.
Chang L, Fang S, Chen Y, Yang Z, Yuan Y, Zhang J, Ye L, Gu W. Inhibition of FASN suppresses the malignant biological behavior of non-small cell lung cancer cells via deregulating glucose metabolism and AKT/ERK pathway. Lipids Health Dis. 2019;18(1):118.PubMedPubMedCentralCrossRef
315.
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.PubMedPubMedCentralCrossRef
316.
Gouw AM, Eberlin LS, Margulis K, Sullivan DK, Toal GG, Tong L, Zare RN, Felsher DW. Oncogene KRAS activates fatty acid synthase, resulting in specific ERK and lipid signatures associated with lung adenocarcinoma. Proc Natl Acad Sci USA. 2017;114(17):4300–5.PubMedPubMedCentralCrossRef
317.
Zhang T, Bai R, Wang Q, Wang K, Li X, Liu K, Ryu J, Wang T, Chang X, Ma W, et al. Fluvastatin inhibits HMG-CoA reductase and prevents non-small cell lung carcinogenesis. Cancer Prev Res. 2019;12(12):837–48 (Phila).CrossRef
318.
Varghese S, Pramanik S, Williams LJ, Hodges HR, Hudgens CW, Fischer GM, Luo CK, Knighton B, Tan L, Lorenzi PL, et al. The glutaminase inhibitor CB-839 (Telaglenastat) enhances the antimelanoma activity of T-cell-mediated immunotherapies. Mol Cancer Ther. 2021;20(3):500–11.PubMedCrossRef
319.
Zhou WX, Chen C, Liu XQ, Li Y, Lin YL, Wu XT, Kong LY, Luo JG. Discovery and optimization of withangulatin a derivatives as novel glutaminase 1 inhibitors for the treatment of triple-negative breast cancer. Eur J Med Chem. 2021;210:112980.PubMedCrossRef
Metadata
Title
TGF-β signaling in the tumor metabolic microenvironment and targeted therapies
Authors
Xueke Shi
Jin Yang
Shuzhi Deng
Hongdan Xu
Deyang Wu
Qingxiang Zeng
Shimeng Wang
Tao Hu
Fanglong Wu
Hongmei Zhou
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2022
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-022-01349-6

Other articles of this Issue 1/2022

Journal of Hematology & Oncology 1/2022 Go to the issue

Research

Allosteric activation of the metabolic enzyme GPD1 inhibits bladder cancer growth via the lysoPC-PAFR-TRPV2 axis

Review

Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management

Correspondence

Immune response to vaccination against SARS-CoV-2 in hematopoietic stem cell transplantation and CAR T-cell therapy recipients

Letter to the Editor

HLF regulates ferroptosis, development and chemoresistance of triple-negative breast cancer by activating tumor cell-macrophage crosstalk

Correction

Correction: Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets

Review

A clinician perspective on the treatment of chronic myeloid leukemia in the chronic phase
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

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
Image Credits