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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2019

Open Access 01-12-2019 | Review

The effects and the mechanisms of autophagy on the cancer-associated fibroblasts in cancer

Authors: Yuanliang Yan, Xi Chen, Xiang Wang, Zijin Zhao, Wenfeng Hu, Shuangshuang Zeng, Jie Wei, Xue Yang, Long Qian, Shuyi Zhou, Lunquan Sun, Zhicheng Gong, Zhijie Xu

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2019

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Abstract

Cancer-associated fibroblasts (CAFs) plays an essential role in cancer cell growth, metabolism and immunoreaction. Autophagy is an intracellular self-degradative process that balances cell energy source and regulates tissue homeostasis. Targeting autophagy has gained interest with multiple preclinical and clinical trials, such as the pharmacological inhibitor chloroquine or the inducer rapamycin, especially in exploiting its ability to modulate the secretory capability of CAFs to enhance drug delivery or inhibit it to prevent its influence on cancer cell chemoresistance. In this review, we summarize the reports on autophagy in cancer-associated fibroblasts by detailing the mechanism and role of autophagy in CAFs, including the hypoxic-autophagy positive feedback cycle, the metabolic cross-talk between CAFs and tumors induced by autophagy, CAFs secreted cytokines promote cancer survival by secretory autophagy, CAFs autophagy-induced EMT, stemness, senescence and treatment sensitivity, as well as the research of antitumor chemicals, miRNAs and lncRNAs. Additionally, we discuss the evidence of molecules in CAFs that are relevant to autophagy and the contribution to sensitive treatments as a potential target for cancer treatment.
Literature
1.
2.
Bravo-San Pedro JM, Kroemer G, Galluzzi L. Autophagy and Mitophagy in cardiovascular disease. Circ Res. 2017;120:1812–24.CrossRefPubMed
3.
Zhang Y, Sowers JR, Ren J. Targeting autophagy in obesity: from pathophysiology to management. Nat Rev Endocrinol. 2018;14:356–76.CrossRefPubMed
4.
Nikoletopoulou V, Tavernarakis N. Regulation and roles of autophagy at synapses. Trends Cell Biol. 2018;28:646–61.CrossRefPubMed
5.
6.
Zhao XL, Lin Y, Jiang J, Tang Z, Yang S, Lu L, Liang Y, Liu X, Tan J, Hu XG, et al. High-mobility group box 1 released by autophagic cancer-associated fibroblasts maintains the stemness of luminal breast cancer cells. J Pathol. 2017;243:376–89.CrossRefPubMedPubMedCentral
7.
Terabe T, Uchida F, Nagai H, Omori S, Ishibashi-Kanno N, Hasegawa S, Yamagata K, Gosho M, Yanagawa T, Bukawa H. Expression of autophagy-related markers at the surgical margin of oral squamous cell carcinoma correlates with poor prognosis and tumor recurrence. Hum Pathol. 2018;73:156–63.CrossRefPubMed
8.
Alers S, Loffler AS, Paasch F, Dieterle AM, Keppeler H, Lauber K, Campbell DG, Fehrenbacher B, Schaller M, Wesselborg S, Stork B. Atg13 and FIP200 act independently of Ulk1 and Ulk2 in autophagy induction. Autophagy. 2011;7:1423–33.CrossRefPubMed
9.
Hosokawa N, Sasaki T, Iemura S, Natsume T, Hara T, Mizushima N. Atg101, a novel mammalian autophagy protein interacting with Atg13. Autophagy. 2009;5:973–9.CrossRefPubMed
10.
Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, Vasquez DS, Joshi A, Gwinn DM, Taylor R, et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science. 2011;331:456–61.CrossRefPubMed
11.
He C, Bassik MC, Moresi V, Sun K, Wei Y, Zou Z, An Z, Loh J, Fisher J, Sun Q, et al. Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature. 2012;481:511–5.CrossRefPubMedPubMedCentral
12.
Dikic I, Elazar Z. Mechanism and medical implications of mammalian autophagy. Nat Rev Mol Cell Biol. 2018;19:349–64.CrossRefPubMed
13.
Chan JS, Tan MJ, Sng MK, Teo Z, Phua T, Choo CC, Li L, Zhu P, Tan NS. Cancer-associated fibroblasts enact field cancerization by promoting extratumoral oxidative stress. Cell Death Dis. 2017;8:e2562.CrossRefPubMedPubMedCentral
14.
Madar S, Goldstein I, Rotter V. 'Cancer associated fibroblasts'--more than meets the eye. Trends Mol Med. 2013;19:447–53.CrossRefPubMed
15.
Cadamuro M, Nardo G, Indraccolo S, Dall'olmo L, Sambado L, Moserle L, Franceschet I, Colledan M, Massani M, Stecca T, et al. Platelet-derived growth factor-D and rho GTPases regulate recruitment of cancer-associated fibroblasts in cholangiocarcinoma. Hepatology. 2013;58:1042–53.CrossRefPubMed
16.
Ishimoto T, Miyake K, Nandi T, Yashiro M, Onishi N, Huang KK, Lin SJ, Kalpana R, Tay ST, Suzuki Y, et al. Activation of transforming growth factor Beta 1 signaling in gastric Cancer-associated fibroblasts increases their motility, via expression of rhomboid 5 homolog 2, and ability to induce invasiveness of gastric Cancer cells. Gastroenterology. 2017;153:191–204 e116.CrossRefPubMed
17.
Paulsson J, Micke P. Prognostic relevance of cancer-associated fibroblasts in human cancer. Semin Cancer Biol. 2014;25:61–8.CrossRefPubMed
18.
Su S, Chen J, Yao H, Liu J, Yu S, Lao L, Wang M, Luo M, Xing Y, Chen F, et al. CD10(+)GPR77(+) Cancer-associated fibroblasts promote Cancer formation and Chemoresistance by sustaining Cancer Stemness. Cell. 2018;172:841–56 e816.CrossRefPubMed
19.
Vaquero J, Lobe C, Tahraoui S, Claperon A, Mergey M, Merabtene F, Wendum D, Coulouarn C, Housset C, Desbois-Mouthon C, et al. The IGF2/IR/IGF1R pathway in tumor cells and Myofibroblasts mediates resistance to EGFR inhibition in cholangiocarcinoma. Clin Cancer Res. 2018;24:4282–96.CrossRefPubMed
20.
Issa AR, Sun J, Petitgas C, Mesquita A, Dulac A, Robin M, Mollereau B, Jenny A, Cherif-Zahar B, Birman S. The lysosomal membrane protein LAMP2A promotes autophagic flux and prevents SNCA-induced Parkinson disease-like symptoms in the Drosophila brain. Autophagy. 2018;14:1898–910.CrossRefPubMedPubMedCentral
21.
Loeffler DA, Klaver AC, Coffey MP, Aasly JO. Cerebrospinal fluid concentration of key autophagy protein Lamp2 changes little during Normal aging. Front Aging Neurosci. 2018;10:130.CrossRefPubMedPubMedCentral
22.
Su HY, Waldron RT, Gong R, Ramanujan VK, Pandol SJ, Lugea A. The Unfolded Protein Response Plays a Predominant Homeostatic Role in Response to Mitochondrial Stress in Pancreatic Stellate Cells. PLoS One. 2016;11:e0148999.CrossRefPubMedPubMedCentral
23.
Sousa CM, Biancur DE, Wang X, Halbrook CJ, Sherman MH, Zhang L, Kremer D, Hwang RF, Witkiewicz AK, Ying H, et al. Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. Nature. 2016;536:479–83.CrossRefPubMedPubMedCentral
24.
Li K, Kang H, Wang Y, Hai T, Rong G, Sun H. Letrozole-induced functional changes in carcinoma-associated fibroblasts and their influence on breast cancer cell biology. Med Oncol. 2016;33:64.CrossRefPubMed
25.
26.
Zhou W, Xu G, Wang Y, Xu Z, Liu X, Xu X, Ren G, Tian K. Oxidative stress induced autophagy in cancer associated fibroblast enhances proliferation and metabolism of colorectal cancer cells. Cell Cycle. 2017;16:73–81.CrossRefPubMed
27.
28.
New J, Arnold L, Ananth M, Alvi S, Thornton M, Werner L, Tawfik O, Dai H, Shnayder Y, Kakarala K, et al. Secretory autophagy in Cancer-associated fibroblasts promotes head and neck Cancer progression and offers a novel therapeutic target. Cancer Res. 2017;77:6679–91.CrossRefPubMedPubMedCentral
29.
Wang M, Zhang J, Huang Y, Ji S, Shao G, Feng S, Chen D, Zhao K, Wang Z, Wu A. Cancer-associated fibroblasts autophagy enhances progression of triple-negative breast Cancer cells. Med Sci Monit. 2017;23:3904–12.CrossRefPubMedPubMedCentral
30.
Ngabire D, Kim GD. Autophagy and inflammatory response in the tumor microenvironment. Int J Mol Sci. 2017;18.
31.
Goruppi S, Jo SH, Laszlo C, Clocchiatti A, Neel V, Dotto GP. Autophagy controls CSL/RBPJkappa stability through a p62/SQSTM1-dependent mechanism. Cell Rep. 2018;24:3108–14 e3104.CrossRefPubMedPubMedCentral
32.
Wang Y, Gan G, Wang B, Wu J, Cao Y, Zhu D, Xu Y, Wang X, Han H, Li X, et al. Cancer-associated fibroblasts promote irradiated Cancer cell recovery through autophagy. EBioMedicine. 2017;17:45–56.CrossRefPubMedPubMedCentral
33.
Sui X, Chen R, Wang Z, Huang Z, Kong N, Zhang M, Han W, Lou F, Yang J, Zhang Q, et al. Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment. Cell Death Dis. 2013;4:e838.CrossRefPubMedPubMedCentral
34.
Liao JK, Zhou B, Zhuang XM, Zhuang PL, Zhang DM, Chen WL. Cancer-associated fi broblasts confer cisplatin resistance of tongue cancer via autophagy activation. Biomed Pharmacother. 2018;97:1341–8.CrossRefPubMed
35.
Pagano G, Talamanca AA, Castello G, Cordero MD, d'Ischia M, Gadaleta MN, Pallardo FV, Petrovic S, Tiano L, Zatterale A. Oxidative stress and mitochondrial dysfunction across broad-ranging pathologies: toward mitochondria-targeted clinical strategies. Oxidative Med Cell Longev. 2014;2014:541230.CrossRef
36.
Lisanti MP, Martinez-Outschoorn UE, Chiavarina B, Pavlides S, Whitaker-Menezes D, Tsirigos A, Witkiewicz A, Lin Z, Balliet R, Howell A, Sotgia F. Understanding the "lethal" drivers of tumor-stroma co-evolution: emerging role(s) for hypoxia, oxidative stress and autophagy/mitophagy in the tumor micro-environment. Cancer Biol Ther. 2010;10:537–42.CrossRefPubMedPubMedCentral
37.
Ketteler J, Panic A, Reis H, Wittka A, Maier P, Herskind C, Yague E, Jendrossek V, Klein D. Progression-related loss of stromal Caveolin 1 levels mediates radiation resistance in prostate carcinoma via the apoptosis inhibitor TRIAP1. J Clin Med. 2019;8.
38.
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;9:3256–76.PubMedPubMedCentral
39.
Martinez-Outschoorn UE, Trimmer C, Lin Z, Whitaker-Menezes D, Chiavarina B, Zhou J, Wang C, Pavlides S, Martinez-Cantarin MP, Capozza F, et al. Autophagy in cancer associated fibroblasts promotes tumor cell survival: role of hypoxia, HIF1 induction and NFkappaB activation in the tumor stromal microenvironment. Cell Cycle. 2010;9:3515–33.CrossRefPubMedPubMedCentral
40.
41.
Pavlides S, Tsirigos A, Migneco G, Whitaker-Menezes D, Chiavarina B, Flomenberg N, Frank PG, Casimiro MC, Wang C, Pestell RG, et al. The autophagic tumor stroma model of cancer: role of oxidative stress and ketone production in fueling tumor cell metabolism. Cell Cycle. 2010;9:3485–505.CrossRefPubMedPubMedCentral
42.
Badura M, Braunstein S, Zavadil J, Schneider RJ. DNA damage and eIF4G1 in breast cancer cells reprogram translation for survival and DNA repair mRNAs. Proc Natl Acad Sci U S A. 2012;109:18767–72.CrossRefPubMedPubMedCentral
43.
Kang R, Tang D, Lotze MT, Zeh HJ 3rd. AGER/RAGE-mediated autophagy promotes pancreatic tumorigenesis and bioenergetics through the IL6-pSTAT3 pathway. Autophagy. 2012;8:989–91.CrossRefPubMedPubMedCentral
44.
Esteve JM, Armengod ME, Knecht E. BRCA1 negatively regulates formation of autophagic vacuoles in MCF-7 breast cancer cells. Exp Cell Res. 2010;316:2618–29.CrossRefPubMed
45.
Salem AF, Howell A, Sartini M, Sotgia F, Lisanti MP. Downregulation of stromal BRCA1 drives breast cancer tumor growth via upregulation of HIF-1alpha, autophagy and ketone body production. Cell Cycle. 2012;11:4167–73.CrossRefPubMedPubMedCentral
46.
Wang Q, Xue L, Zhang X, Bu S, Zhu X, Lai D. Autophagy protects ovarian cancer-associated fibroblasts against oxidative stress. Cell Cycle. 2016;15:1376–85.CrossRefPubMedPubMedCentral
47.
Chen WJ, Ho CC, Chang YL, Chen HY, Lin CA, Ling TY, Yu SL, Yuan SS, Chen YJ, Lin CY, et al. Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via paracrine signalling. Nat Commun. 2014;5:3472.CrossRefPubMed
48.
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;8:3984–4001.CrossRefPubMed
49.
Chiavarina B, Whitaker-Menezes D, Martinez-Outschoorn UE, Witkiewicz AK, Birbe R, Howell A, Pestell RG, Smith J, Daniel R, Sotgia F, Lisanti MP. Pyruvate kinase expression (PKM1 and PKM2) in cancer-associated fibroblasts drives stromal nutrient production and tumor growth. Cancer Biol Ther. 2011;12:1101–13.CrossRefPubMedPubMedCentral
50.
Avena P, Anselmo W, Whitaker-Menezes D, Wang C, Pestell RG, Lamb RS, Hulit J, Casaburi I, Ando S, Martinez-Outschoorn UE, et al. Compartment-specific activation of PPARgamma governs breast cancer tumor growth, via metabolic reprogramming and symbiosis. Cell Cycle. 2013;12:1360–70.CrossRefPubMedPubMedCentral
51.
Lee JJ, Drakaki A, Iliopoulos D, Struhl K. MiR-27b targets PPARgamma to inhibit growth, tumor progression and the inflammatory response in neuroblastoma cells. Oncogene. 2012;31:3818–25.CrossRefPubMed
52.
Zhu B, Ferry CH, Blazanin N, Bility MT, Khozoie C, Kang BH, Glick AB, Gonzalez FJ, Peters JM. PPARbeta/delta promotes HRAS-induced senescence and tumor suppression by potentiating p-ERK and repressing p-AKT signaling. Oncogene. 2014;33:5348–59.CrossRefPubMed
53.
Genc GE, Hipolito VEB, Botelho RJ, Gumuslu S. Lysophosphatidic acid represses autophagy in prostate carcinoma cells. Biochem Cell Biol. 2018.
54.
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.CrossRefPubMed
55.
Schnittert J, Heinrich MA, Kuninty PR, Storm G, Prakash J. Reprogramming tumor stroma using an endogenous lipid lipoxin A4 to treat pancreatic cancer. Cancer Lett. 2018;420:247–58.CrossRefPubMed
56.
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.CrossRefPubMedPubMedCentral
57.
Serrao EM, Kettunen MI, Rodrigues TB, Dzien P, Wright AJ, Gopinathan A, Gallagher FA, Lewis DY, Frese KK, Almeida J, et al. MRI with hyperpolarised [1-13C]pyruvate detects advanced pancreatic preneoplasia prior to invasive disease in a mouse model. Gut. 2016;65:465–75.CrossRefPubMed
58.
Chaudhri VK, Salzler GG, Dick SA, Buckman MS, Sordella R, Karoly ED, Mohney R, Stiles BM, Elemento O, Altorki NK, McGraw TE. Metabolic alterations in lung cancer-associated fibroblasts correlated with increased glycolytic metabolism of the tumor. Mol Cancer Res. 2013;11:579–92.CrossRefPubMedPubMedCentral
59.
Veyel D, Sokolowska EM, Moreno JC, Kierszniowska S, Cichon J, Wojciechowska I, Luzarowski M, Kosmacz M, Szlachetko J, Gorka M, et al. PROMIS, global analysis of PROtein-metabolite interactions using size separation in Arabidopsis thaliana. J Biol Chem. 2018;293:12440–53.CrossRefPubMedPubMedCentral
60.
Katheder NS, Khezri R, O'Farrell F, Schultz SW, Jain A, Rahman MM, Schink KO, Theodossiou TA, Johansen T, Juhasz G, et al. Microenvironmental autophagy promotes tumour growth. Nature. 2017;541:417–20.CrossRefPubMedPubMedCentral
61.
Folkerts H, Hilgendorf S, Vellenga E, Bremer E, Wiersma VR. The multifaceted role of autophagy in cancer and the microenvironment. Med Res Rev. 2018.
62.
Song X, Said Q, Tran O, Krueger DA, Bissler J. Everolimus compliance and persistence among tuberous sclerosis complex patients with renal angiomyolipoma or subependymal giant cell astrocytoma. Curr Med Res Opin. 2018:1–18.
63.
Thuwajit C, Ferraresi A, Titone R, Thuwajit P, Isidoro C. The metabolic cross-talk between epithelial cancer cells and stromal fibroblasts in ovarian cancer progression: autophagy plays a role. Med Res Rev. 2018;38:1235–54.CrossRefPubMed
64.
Kimura T, Jia J, Claude-Taupin A, Kumar S, Choi SW, Gu Y, Mudd M, Dupont N, Jiang S, Peters R, et al. Cellular and molecular mechanism for secretory autophagy. Autophagy. 2017;13:1084–5.CrossRefPubMedPubMedCentral
65.
von Ahrens D, Bhagat TD, Nagrath D, Maitra A, Verma A. The role of stromal cancer-associated fibroblasts in pancreatic cancer. J Hematol Oncol. 2017;10:76.CrossRef
66.
Lu H, Han M, Yuan X, Tursun K, Zhang Y, Li Y, Li Z, Feng S, Zhou L, Pan Z, et al. Role of IL-6-mediated expression of NS5ATP9 in autophagy of liver cancer cells. J Cell Physiol. 2018;233:9312–9.CrossRefPubMed
67.
Nuchel J, Ghatak S, Zuk AV, Illerhaus A, Morgelin M, Schonborn K, Blumbach K, Wickstrom SA, Krieg T, Sengle G, et al. TGFB1 is secreted through an unconventional pathway dependent on the autophagic machinery and cytoskeletal regulators. Autophagy. 2018;14:465–86.CrossRefPubMedPubMedCentral
68.
Thongchot S, Ferraresi A, Vidoni C, Loilome W, Yongvanit P, Namwat N, Isidoro C. Resveratrol interrupts the pro-invasive communication between cancer associated fibroblasts and cholangiocarcinoma cells. Cancer Lett. 2018;430:160–71.CrossRefPubMed
69.
Ferraresi A, Phadngam S, Morani F, Galetto A, Alabiso O, Chiorino G, Isidoro C. Resveratrol inhibits IL-6-induced ovarian cancer cell migration through epigenetic up-regulation of autophagy. Mol Carcinog. 2017;56:1164–81.CrossRefPubMed
70.
Frassanito MA, De Veirman K, Desantis V, Di Marzo L, Vergara D, Ruggieri S, Annese T, Nico B, Menu E, Catacchio I, et al. Halting pro-survival autophagy by TGFbeta inhibition in bone marrow fibroblasts overcomes bortezomib resistance in multiple myeloma patients. Leukemia. 2016;30:640–8.CrossRefPubMed
71.
Li WL, Xiong LX, Shi XY, Xiao L, Qi GY, Meng C. IKKbeta/NFkappaBp65 activated by interleukin-13 targets the autophagy-related genes LC3B and beclin 1 in fibroblasts co-cultured with breast cancer cells. Exp Ther Med. 2016;11:1259–64.CrossRefPubMedPubMedCentral
72.
Pestell TG, Jiao X, Kumar M, Peck AR, Prisco M, Deng S, Li Z, Ertel A, Casimiro MC, Ju X, et al. Stromal cyclin D1 promotes heterotypic immune signaling and breast cancer growth. Oncotarget. 2017;8:81754–75.CrossRefPubMedPubMedCentral
73.
Zhang X, Schonrogge M, Eichberg J, Wendt EHU, Kumstel S, Stenzel J, Lindner T, Jaster R, Krause BJ, Vollmar B, Zechner D. Blocking autophagy in Cancer-associated fibroblasts supports chemotherapy of pancreatic Cancer cells. Front Oncol. 2018;8:590.CrossRefPubMedPubMedCentral
74.
Liang L, Luo H, He Q, You Y, Fan Y, Liang J. Investigation of cancer-associated fibroblasts and p62 expression in oral cancer before and after chemotherapy. J Craniomaxillofac Surg. 2018;46:605–10.CrossRefPubMed
75.
Molejon MI, Swayden M, Fanale D, Bintz J, Gayet O, Soubeyran P, Iovanna J. Chloroquine plays a cell-dependent role in the response to treatment of pancreatic adenocarcinoma. Oncotarget. 2018;9:30837–46.CrossRefPubMedPubMedCentral
76.
Kong EY, Cheng SH, Yu KN. Induction of autophagy and interleukin 6 secretion in bystander cells: metabolic cooperation for radiation-induced rescue effect? J Radiat Res. 2018;59:129–40.CrossRefPubMedPubMedCentral
77.
Soon PS, Kim E, Pon CK, Gill AJ, Moore K, Spillane AJ, Benn DE, Baxter RC. Breast cancer-associated fibroblasts induce epithelial-to-mesenchymal transition in breast cancer cells. Endocr Relat Cancer. 2013;20:1–12.CrossRefPubMed
78.
Peters S, Stahel RA, Bubendorf L, Bonomi P, Villegas A, Kowalski DM, Baik CS, Isla D, de Castro CJ, Garrido P, et al. Trastuzumab Emtansine (T-DM1) in patients with previously treated HER2-overexpressing metastatic non-small cell lung Cancer: efficacy, Safety and Biomarkers. Clin Cancer Res. 2018.
79.
Wang J, Vasaikar S, Shi Z, Greer M, Zhang B. WebGestalt 2017: A more comprehensive, powerful, flexible and interactive gene set enrichment analysis toolkit. Nucleic Acids Res. 2017;45:W130–7.CrossRefPubMedPubMedCentral
80.
Mink SR, Vashistha S, Zhang W, Hodge A, Agus DB, Jain A. Cancer-associated fibroblasts derived from EGFR-TKI-resistant tumors reverse EGFR pathway inhibition by EGFR-TKIs. Mol Cancer Res. 2010;8:809–20.CrossRefPubMedPubMedCentral
81.
Tallerico R, Garofalo C, Carbone E. A New biological feature of natural killer cells: the recognition of solid tumor-derived Cancer stem cells. Front Immunol. 2016;7:179.CrossRefPubMedPubMedCentral
82.
Busch S, Acar A, Magnusson Y, Gregersson P, Ryden L, Landberg G. TGF-beta receptor type-2 expression in cancer-associated fibroblasts regulates breast cancer cell growth and survival and is a prognostic marker in pre-menopausal breast cancer. Oncogene. 2015;34:27–38.CrossRefPubMed
83.
Komohara Y, Takeya M. CAFs and TAMs: maestros of the tumour microenvironment. J Pathol. 2017;241:313–5.CrossRefPubMed
84.
Narita M, Young AR, Narita M. Autophagy facilitates oncogene-induced senescence. Autophagy. 2009;5:1046–7.CrossRefPubMed
85.
Capparelli C, Guido C, Whitaker-Menezes D, Bonuccelli G, Balliet R, Pestell TG, Goldberg AF, Pestell RG, Howell A, Sneddon S, et al. Autophagy and senescence in cancer-associated fibroblasts metabolically supports tumor growth and metastasis via glycolysis and ketone production. Cell Cycle. 2012;11:2285–302.CrossRefPubMedPubMedCentral
86.
Capparelli C, Whitaker-Menezes D, Guido C, Balliet R, Pestell TG, Howell A, Sneddon S, Pestell RG, Martinez-Outschoorn U, Lisanti MP, Sotgia F. CTGF drives autophagy, glycolysis and senescence in cancer-associated fibroblasts via HIF1 activation, metabolically promoting tumor growth. Cell Cycle. 2012;11:2272–84.CrossRefPubMedPubMedCentral
87.
Capparelli C, Chiavarina B, Whitaker-Menezes D, Pestell TG, Pestell RG, Hulit J, Ando S, Howell A, Martinez-Outschoorn UE, Sotgia F, Lisanti MP. CDK inhibitors (p16/p19/p21) induce senescence and autophagy in cancer-associated fibroblasts, "fueling" tumor growth via paracrine interactions, without an increase in neo-angiogenesis. Cell Cycle. 2012;11:3599–610.CrossRefPubMedPubMedCentral
88.
89.
90.
Yan Y, Xu Z, Li Z, Sun L, Gong Z. An insight into the increasing role of LncRNAs in the pathogenesis of gliomas. Front Mol Neurosci. 2017;10:53.PubMedPubMedCentral
91.
Yang X, Xu X, Zhu J, Zhang S, Wu Y, Wu Y, Zhao K, Xing C, Cao J, Zhu H, et al. miR-31 affects colorectal cancer cells by inhibiting autophagy in cancer-associated fibroblasts. Oncotarget. 2016;7:79617–28.PubMedPubMedCentral
92.
Hu J, Zhang L, Mei Z, Jiang Y, Yi Y, Liu L, Meng Y, Zhou L, Zeng J, Wu H, Jiang X. Interaction of E3 ubiquitin ligase MARCH7 with long noncoding RNA MALAT1 and autophagy-related protein ATG7 promotes autophagy and invasion in ovarian Cancer. Cell Physiol Biochem. 2018;47:654–66.CrossRefPubMed
93.
Ding L, Ren J, Zhang D, Li Y, Huang X, Hu Q, Wang H, Song Y, Ni Y, Hou Y. A novel stromal lncRNA signature reprograms fibroblasts to promote the growth of oral squamous cell carcinoma via LncRNA-CAF/interleukin-33. Carcinogenesis. 2018;39:397–406.CrossRefPubMed
94.
Li S, Wu Y, Ding Y, Yu M, Ai Z. CerS6 regulates cisplatin resistance in oral squamous cell carcinoma by altering mitochondrial fission and autophagy. J Cell Physiol. 2018.
95.
Dyczynski M, Yu Y, Otrocka M, Parpal S, Braga T, Henley AB, Zazzi H, Lerner M, Wennerberg K, Viklund J, et al. Targeting autophagy by small molecule inhibitors of vacuolar protein sorting 34 (Vps34) improves the sensitivity of breast cancer cells to Sunitinib. Cancer Lett. 2018;435:32–43.CrossRefPubMed
96.
Wu D, Zhuo L, Wang X. Metabolic reprogramming of carcinoma-associated fibroblasts and its impact on metabolic heterogeneity of tumors. Semin Cell Dev Biol. 2017;64:125–31.CrossRefPubMed
97.
Magda D, Lecane P, Wang Z, Hu W, Thiemann P, Ma X, Dranchak PK, Wang X, Lynch V, Wei W, et al. Synthesis and anticancer properties of water-soluble zinc ionophores. Cancer Res. 2008;68:5318–25.CrossRefPubMedPubMedCentral
98.
Kim KW, Mutter RW, Cao C, Albert JM, Freeman M, Hallahan DE, Lu B. Autophagy for cancer therapy through inhibition of pro-apoptotic proteins and mammalian target of rapamycin signaling. J Biol Chem. 2006;281:36883–90.CrossRefPubMed
99.
Kim KW, Speirs CK, Jung DK, Lu B. The zinc ionophore PCI-5002 radiosensitizes non-small cell lung cancer cells by enhancing autophagic cell death. J Thorac Oncol. 2011;6:1542–52.CrossRefPubMed
100.
Goruppi S, Clocchiatti A, Dotto GP. A role for stromal autophagy in cancer-associated fibroblast activation. Autophagy. 2019.
101.
Martinez-Outschoorn UE, Lisanti MP, Sotgia F. Catabolic cancer-associated fibroblasts transfer energy and biomass to anabolic cancer cells, fueling tumor growth. Semin Cancer Biol. 2014;25:47–60.CrossRefPubMed
102.
He Y, Zhao X, Gao J, Fan L, Yang G, Cho WC, Chen H. Quantum dots-based immunofluorescent imaging of stromal fibroblasts Caveolin-1 and light chain 3B expression and identification of their clinical significance in human gastric cancer. Int J Mol Sci. 2012;13:13764–80.CrossRefPubMedPubMedCentral
103.
104.
Zhang N, Wu Y, Lyu X, Li B, Yan X, Xiong H, Li X, Huang G, Zeng Y, Zhang Y, et al. HSF1 upregulates ATG4B expression and enhances epirubicin-induced protective autophagy in hepatocellular carcinoma cells. Cancer Lett. 2017;409:81–90.CrossRefPubMed
105.
Watanabe Y, Tsujimura A, Taguchi K, Tanaka M. HSF1 stress response pathway regulates autophagy receptor SQSTM1/p62-associated proteostasis. Autophagy. 2017;13:133–48.CrossRefPubMed
106.
Scherz-Shouval R, Santagata S, Mendillo ML, Sholl LM, Ben-Aharon I, Beck AH, Dias-Santagata D, Koeva M, Stemmer SM, Whitesell L, Lindquist S. The reprogramming of tumor stroma by HSF1 is a potent enabler of malignancy. Cell. 2014;158:564–78.CrossRefPubMedPubMedCentral
107.
Goruppi S, Procopio MG, Jo S, Clocchiatti A, Neel V, Dotto GP. The ULK3 kinase is critical for convergent control of Cancer-associated fibroblast activation by CSL and GLI. Cell Rep. 2017;20:2468–79.CrossRefPubMedPubMedCentral
108.
You J, Li M, Tan Y, Cao L, Gu Q, Yang H, Hu C. Snail1-expressing cancer-associated fibroblasts induce lung cancer cell epithelial-mesenchymal transition through miR-33b. Oncotarget. 2017;8:114769–86.PubMedPubMedCentral
109.
Ma LJ, Wang XY, Duan M, Liu LZ, Shi JY, Dong LQ, Yang LX, Wang ZC, Ding ZB, Ke AW, et al. Telomere length variation in tumor cells and cancer-associated fibroblasts: potential biomarker for hepatocellular carcinoma. J Pathol. 2017;243:407–17.CrossRefPubMedPubMedCentral
110.
Moinfar F, Man YG, Arnould L, Bratthauer GL, Ratschek M, Tavassoli FA. Concurrent and independent genetic alterations in the stromal and epithelial cells of mammary carcinoma: implications for tumorigenesis. Cancer Res. 2000;60:2562–6.PubMed
111.
Galluzzi L, Baehrecke EH, Ballabio A, Boya P, Bravo-San Pedro JM, Cecconi F, Choi AM, Chu CT, Codogno P, Colombo MI, et al. Molecular definitions of autophagy and related processes. EMBO J. 2017;36:1811–36.CrossRefPubMedPubMedCentral
112.
Turley SJ, Cremasco V, Astarita JL. Immunological hallmarks of stromal cells in the tumour microenvironment. Nat Rev Immunol. 2015;15:669–82.CrossRefPubMed
113.
Purcell JW, Tanlimco SG, Hickson J, Fox M, Sho M, Durkin L, Uziel T, Powers R, Foster K, McGonigal T, et al. LRRC15 is a novel mesenchymal protein and stromal target for antibody-drug conjugates. Cancer Res. 2018;78:4059–72.CrossRefPubMed
114.
Erkan M, Hausmann S, Michalski CW, Fingerle AA, Dobritz M, Kleeff J, Friess H. The role of stroma in pancreatic cancer: diagnostic and therapeutic implications. Nat Rev Gastroenterol Hepatol. 2012;9:454–67.CrossRefPubMed
115.
Doostan I, Karakas C, Kohansal M, Low KH, Ellis MJ, Olson JA Jr, Suman VJ, Hunt KK, Moulder SL, Keyomarsi K. Cytoplasmic cyclin E mediates resistance to aromatase inhibitors in breast Cancer. Clin Cancer Res. 2017;23:7288–300.CrossRefPubMedPubMedCentral
116.
Guo ML, Liao K, Periyasamy P, Yang L, Cai Y, Callen SE, Buch S. Cocaine-mediated microglial activation involves the ER stress-autophagy axis. Autophagy. 2015;11:995–1009.CrossRefPubMedPubMedCentral
117.
Deng X, Luo S, Luo X, Hu M, Ma F, Wang Y, Lai X, Zhou L. Polysaccharides from Chinese herbal Lycium barbarum induced systemic and local immune responses in H22 tumor-bearing mice. J Immunol Res. 2018;2018:3431782.PubMedPubMedCentral
118.
Han SY, Hu MH, Qi GY, Ma CX, Wang YY, Ma FL, Tao N, Qin ZH. Polysaccharides from Polygonatum inhibit the proliferation of prostate Cancer-associated fibroblasts. Asian Pac J Cancer Prev. 2016;17:3829–33.PubMed
Metadata
Title
The effects and the mechanisms of autophagy on the cancer-associated fibroblasts in cancer
Authors
Yuanliang Yan
Xi Chen
Xiang Wang
Zijin Zhao
Wenfeng Hu
Shuangshuang Zeng
Jie Wei
Xue Yang
Long Qian
Shuyi Zhou
Lunquan Sun
Zhicheng Gong
Zhijie Xu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2019
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-019-1172-5

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