A Summary of Autophagy Mechanisms in Cancer Cells

Main Article Content

Reza Sahebi
Nazanin Akbari
Zeynab Bayat
Mohammad Rashidmayvan
Amin Mansoori
Maria Beihaghi

Abstract

Autophagy is a well-known vital process in cells and plays a significant role in biological evolution, the immune system, and cell death. It can be effective in fatal disorders, such as nervous system degeneration, autoimmune diseases, and cancer. Autophagy has a dual role; on the one hand, it increases cell survival, and on the other hand, it causes cell death in advanced stages although no agreement has yet been accomplished on the role of autophagy in cellular processes. There is evidence that autophagic signaling regulation is inversely related to oncogenic signaling. Numerous commonly activated oncogenes (class I PtdIns3K, Akt, TOR, Bcl-2) inhibit autophagy, while commonly mutated or epigenetically silenced tumor suppressor genes (p53, PTEN, TSC1/TSC2) promote autophagy. Autophagy promotes cancer progression by supplying sufficient nutrients that enable cancer cell growth. FIP200, a related- autophagy protein, interacts with ATG 13 and induces autophagy. Increased autophagy causes the interaction of Becklin 118 with HER2, resulting in an increase in tumorigenesis. In order to make complete use of the autophagic properties in cancer treatment, further studies on its role in disease in the different biologics fields are essential. Cancer stem cells (CSCs) can regenerate, cause cancer, and enhance resistance to treatment, metastasis, and recurrence. Autophagy moderates stressful conditions and promotes resistance to anticancer therapy. In addition, autophagy regulates the ability of radiation in CSCs and leads to failure in anticancer therapies. Hence, autophagy is a potential therapeutic target for metastasis resistance and anticancer therapy recurrence. Regulation of autophagy using autophagy modulators alone does not improve the therapeutic effects of anticancer reagents. In contrast, it has supplied nutrients for cancer cells. Consequently, clinical trials aiming for autophagy through a combination of autophagy modulations and anticancer reagents are crucial to consider autophagy as a potentially effective therapeutic strategy in anticancer therapy.

Article Details

How to Cite
Sahebi, R., Akbari, N., Bayat, Z., Rashidmayvan, M., Mansoori, A., & Beihaghi, M. (2022). A Summary of Autophagy Mechanisms in Cancer Cells. Research in Biotechnology and Environmental Science, 1(1), 28–35. https://doi.org/10.58803/RBES.2022.1.1.06
Section
Reveiw Article

References

Parzych KR and Klionsky DJ. An overview of autophagy: Morphology, mechanism, and regulation. Antioxid Redox Signal. 2014; 20(3): 460-73. DOI: https://doi.org/10.1089/ars.2013.5371

Yang Z and Klionsky DJ. Mammalian autophagy: Core molecular machinery and signaling regulation. Curr Opin Cell Biol. 2010; 22: 124-131. DOI: https://doi.org/10.1016/j.ceb.2009.11.014

Teng S, Li MY, Li PF, and Cao JM. Micro RNAs in cardiac autophagy: Small molecules and big role. Cells. 2018; 7(8): 104. DOI: https://doi.org/10.3390/cells7080104

Li X, He S, and Ma B. Autophagy and autophagy-related proteins in cancer. Mol Cancer. 2020; 19(1): 12. DOI: https://doi.org/10.1186/s12943-020-1138-4

Rajawat YS, Hilioti Z, and Bossis I. Aging: Central role for autophagy and the lysosomal degradative system. Ageing Res Rev. 2009; 8(3): 199-213. DOI: https://doi.org/10.1016/j.arr.2009.05.001

White E (2012). Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer. 12(6): 401-410. DOI: https://doi.org/10.1038/nrc3262

Gozuacik D and Kimchi A. Autophagy as a cell death and tumor suppressor mechanism. Oncogene. 2004; 23(16): 2891-2906. DOI: https://doi.org/10.1038/sj.onc.1207521

Bampton ETW, Goemans CG, Niranjan D, Mizushima N, and Tolkovsky AM. The dynamics of autophagy visualised in live cells: From autophagosome formation to fusion with endo/lysosomes. Autophagy. 2005; 1(1): 23-36. DOI: https://doi.org/10.4161/auto.1.1.1495

Tanida I, Ueno T, and Kominami E. LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol. 2004; 36(12): 2503-2518. DOI: https://doi.org/10.1016/j.biocel.2004.05.009

Xu HD and Qin ZH. Beclin 1, Bcl-2 and autophagy. Adv Exp Med Biol. 2019; 1206: 109-126. DOI: https://doi.org/10.1007/978-981-15-0602-4_5

Chavez-Dominguez R, Perez-Medina M, Lopez-Gonzalez JS, Galicia-Velasco M, and Aguilar-Cazares D. The double-edge sword of autophagy in cancer: from tumor suppression to pro-tumor activity. Front Oncol. 2020; 10: 578418. DOI: https://doi.org/10.3389/fonc.2020.578418

Chang YT, Tseng HC, Huang CC, Chen YP, Chiang HC, and Chou FP. Relative down‐regulation of apoptosis and autophagy genes in colorectal cancer. Eur J Clin Invest. 2011; 41(1): 84-92. DOI: https://doi.org/10.1111/j.1365-2362.2010.02383.x

Kenific CM and Debnath J. Cellular and metabolic functions for autophagy in cancer cells. Trends Cell Biol. 2015; 25(1): 37-45. DOI: https://doi.org/10.1016/j.tcb.2014.09.001

Choi KS. Autophagy and cancer. Exp Mol Med. 2012; 44(2): 109-120. Available at: https://www.nature.com/articles/emm201215

Kabeya Y, Kamada Y, Baba M, Takikawa H, Sasaki M, and Ohsumi Y. Atg17 functions in cooperation with Atg1 and Atg13 in yeast autophagy. Mol Biol Cell. 2005; 16(5): 2544-2553. DOI: https://doi.org/10.1091/mbc.e04-08-0669

Lorin S, Hamaï A, Mehrpour M, and Codogno P. Autophagy regulation and its role in cancer. Semin Cancer Biol. 2013; 23(5): 361-379. DOI: https://doi.org/10.1016/j.semcancer.2013.06.007

Ré AE, Fernández-Barrena MG, Almada LL, Mills LD, Elsawa SF, Lund G, et al. Novel AKT1-GLI3-VMP1 pathway mediates KRAS oncogene-induced autophagy in cancer cells. J Biol Chem. 2012; 287(30): 25325-25334. DOI: https://doi.org/10.1074/jbc.m112.370809

Nitsche BM, Burggraaf-van Welzen AM, Lamers G, Meyer V, and Ram AF. Autophagy promotes survival in aging submerged cultures of the filamentous fungus Aspergillus niger. Appl Microbiol Biotechnol. 2013; 97(18): 8205-8218. DOI: https://doi.org/10.1007/s00253-013-4971-1

Wen X, Wu J, Wang F, Liu B, Huang C, and Wei Y. Deconvoluting the role of reactive oxygen species and autophagy in human diseases. Free Radic Biol Med. 2013; 65: 402-410. DOI: https://doi.org/10.1016/j.freeradbiomed.2013.07.013

Redza-Dutordoir M and Averill-Bates DA. Interactions between reactive oxygen species and autophagy: Special issue: Death mechanisms in cellular homeostasis. Biochim Biophys Acta Mol Cell Res. 2021; 1868(8): 119041. DOI: https://doi.org/10.1016/j.bbamcr.2021.119041

Mannan A, Germon ZP, Chamberlain J, Sillar JR, Nixon B, and Dun MD. Reactive oxygen species in acute lymphoblastic leukaemia: Reducing radicals to refine responses. Antioxidants. 2021; 10(10): 1616. DOI: https://doi.org/10.3390/antiox10101616

Haruki K, Kosumi K, Hamada T, Twombly TS, Väyrynen JP, Kim SA, et al. Association of autophagy status with amount of Fusobacterium nucleatum in colorectal cancer. J Pathol. 2020; 250(4): 397-408. DOI: https://doi.org/10.1002/path.5381

Yun CW and Lee SH. The roles of autophagy in cancer. Int J Mol Sci. 2018; 19(11): 3466. DOI: https://doi.org/10.3390/ijms19113466

Eskelinen EL, Kageyama S, and Komatsu M. p62/SQSTM1 droplets initiate autophagosome biogenesis and oxidative stress control. Mol Cell Oncol. 2021; 8(2): 1890990. DOI: https://doi.org/10.1080/23723556.2021.1890990

Tian Y, Song W, Li D, Cai L, and Zhao Y. Resveratrol as a natural regulator of autophagy for prevention and treatment of cancer. Onco Targets Ther. 2019; 12: 8601-8609. DOI: https://doi.org/10.2147/ott.s213043

Revathidevi S and Munirajan AK. Akt in cancer: Mediator and more. Semin Cancer Biol. 2019; 59: 80-91. DOI: https://doi.org/10.1016/j.semcancer.2019.06.002

Zhang J, Zhang S, Shi Q, Allen TD, You F, and Yang D. The anti-apoptotic proteins Bcl-2 and Bcl-xL suppress Beclin 1/Atg6-mediated lethal autophagy in polyploid cells. Exp Cell Res. 2020; 394(1): 112112. DOI: https://doi.org/10.1016/j.yexcr.2020.112112

Usman RM, Razzaq F, Akbar A, Farooqui AA, Iftikhar A, Latif A, et al. Role and mechanism of autophagy‐regulating factors in tumorigenesis and drug resistance. Asia Pac J Clin Oncol. 2021; 17(3): 193-208. DOI: https://doi.org/10.1111/ajco.13449

Kaur S and Changotra H. The beclin 1 interactome: Modification and roles in the pathology of autophagy-related disorders. Biochimie. 2020; 175: 34-49. DOI: https://doi.org/10.1016/j.biochi.2020.04.025

Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A, et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest. 2003; 112(12): 1809-1820. DOI: https://doi.org/10.1172/JCI20039

Nasb M, Kirberger M, and Chen N. Molecular processes and regulation of autophagy. In: Chen N, editor. Exercise, autophagy and chronic diseases. Springer, Singapore; 2021; p. 1-27. DOI: https://doi.org/10.1007/978-981-16-4525-9_1

Yerbury JJ, Ooi L, Dillin A, Saunders DN, Hatters DM, Beart PM, et al. Walking the tightrope: Proteostasis and neurodegenerative disease. J Neurochem. 2016; 137(4): 489-505. DOI: https://doi.org/10.1111/jnc.13575

Reggiori F, Komatsu M, Finley K, and Simonsen A. Autophagy: More than a nonselective pathway. Int J Cell Biol. 2012; 2012: 219625. DOI: https://doi.org/10.1155/2012/219625

Udristioiu A and Nica-Badea D. Autophagy dysfunctions associated with cancer cells and their therapeutic implications. Biomed Pharmacother. 2019; 115: 108892. DOI: https://doi.org/10.1016/j.biopha.2019.108892

White E. The role for autophagy in cancer. J Clin Investig. 2015; 125(1): 42-46. DOI: https://doi.org/10.1172/JCI73941

Antunes F, Erustes AG, Costa AJ, Nascimento AC, Bincoletto C, Ureshino RP, et al. Autophagy and intermittent fasting: The connection for cancer therapy?. Clinics. 2018; 73(Suppl 1): e814s. DOI: https://doi.org/10.6061/clinics/2018/e814s

Maiuri MC, Tasdemir E, Criollo A, Morselli E, Vicencio JM, Carnuccio R, et al. Control of autophagy by oncogenes and tumor suppressor genes. Cell Death Differ. 2009; 16(1): 87-93. DOI: https://doi.org/10.1038/cdd.2008.131

Ariosa AR, Lahiri V, Lei Y, Yang Y, Yin Z, Zhang Z, et al. A perspective on the role of autophagy in cancer. Biochim Biophys Acta Mol Basis Dis. 2021; 1867(12): 166262. DOI: https://doi.org/10.1016/j.bbadis.2021.166262

Levy JM, Towers CG, and Thorburn A. Targeting autophagy in cancer. Nat Rev Cancer. 2017; 17(9): 528-542. Available at: https://www.nature.com/articles/nrc.2017.53

Chen HY and White E. Role of autophagy in cancer prevention. Cancer Prev Res. 2011; 4(7): 973-983. DOI: https://doi.org/10.1158/1940-6207.capr-10-0387

Yang ZJ, Chee CE, Huang S, and Sinicrope FA. The role of autophagy in cancer: Therapeutic implications. Mol Cancer Ther. 2011; 10(9): 1533-1541. DOI: https://doi.org/10.1158/1535-7163.mct-11-0047

Zhao H, Ming T, Tang S, Ren S, Yang H, Liu M, et al. Wnt signaling in colorectal cancer: Pathogenic role and therapeutic target. Mol Cancer. 2022; 21(1): 144. DOI: https://doi.org/10.1186/s12943-022-01616-7

Chen N and Karantza-Wadsworth V. Role and regulation of autophagy in cancer. Biochim Biophys Acta. 2009; 1793(9): 1516-1523. DOI: https://doi.org/10.1016/j.bbamcr.2008.12.013

Moscat J and Diaz-Meco MT. p62 at the crossroads of autophagy, apoptosis, and cancer. Cell. 2009; 137(6): 1001-1004. DOI: https://doi.org/10.1016/j.cell.2009.05.023

Zhong Z, Sanchez-Lopez E, and Karin M. Autophagy, inflammation, and immunity: A troika governing cancer and its treatment. Cell. 2016; 166(2): 288-298. DOI: https://doi.org/10.1016/j.cell.2016.05.051

Yessenkyzy A, Saliev T, Zhanaliyeva M, Masoud AR, Umbayev B, Sergazy S, et al. Polyphenols as caloric-restriction mimetics and autophagy inducers in aging research. Nutrients. 2020; 12(5): 1344. DOI: https://doi.org/10.3390/nu12051344

Pietrocola F, Pol J, Vacchelli E, Baracco EE, Levesque S, Castoldi F, et al. Autophagy induction for the treatment of cancer. Autophagy. 2016; 12(10): 1962-1964.

Shi TT, Yu XX, Yan LJ, and Xiao HT. Research progress of hydroxychloroquine and autophagy inhibitors on cancer. Cancer Chemother Pharmacol. 2017; 79(2): 287-924. DOI: https://doi.org/10.1007/s00280-016-3197-1

Udristioiu A and Nica-Badea D. Autophagy dysfunctions associated with cancer cells and their therapeutic implications. Biomed Pharmacot. 2019; 115: 108892. DOI: https://doi.org/10.1016/j.biopha.2019.108892

Vidoni C, Ferraresi A, Esposito A, Maheshwari C, Dhanasekaran DN, Mollace V, et al. Calorie restriction for cancer prevention and therapy: mechanisms, expectations, and efficacy. J Cancer Prev. 2021; 26(4): 224-236. DOI: https://doi.org/10.15430/jcp.2021.26.4.224

Desai A, Yan Y, and Gerson SL. Concise reviews: Cancer stem cell targeted therapies: Toward clinical success. Stem Cells Transl Med. 2019; 8(1): 75-81. DOI: https://doi.org/10.1002/sctm.18-0123

Nazio F, Bordi M, Cianfanelli V, Locatelli F, and Cecconi F. Autophagy and cancer stem cells: Molecular mechanisms and therapeutic applications. Cell Death & Differentiation. 2019; 26(4): 690-702. Available at: https://www.nature.com/articles/s41418-019-0292-y

Smith AG and Macleod KF. Autophagy, cancer stem cells and

drug resistance. The J Pathol. 2019; 247(5): 708-718. DOI: https://doi.org/10.1002/path.5222

Zhao Y, Huang Q, Yang J, Lou M, Wang A, Dong J, et al. Autophagy impairment inhibits differentiation of glioma stem/progenitor cells. Brain Res. 2010; 1313: 250-258. DOI: https://doi.org/10.1016/j.brainres.2009.12.004

Huang X, Bai HM, Chen L, Li B, and Lu YC. Reduced expression of LC3B-II and Beclin 1 in glioblastoma multiforme indicates a down-regulated autophagic capacity that relates to the progression of astrocytic tumors. J Clin Neurosci. 2010; 17(12): 1515-1519. DOI: https://doi.org/10.1016/j.jocn.2010.03.051

Gangopadhyay S, Nandy A, Hor P, and Mukhopadhyay A. Breast cancer stem cells: A novel therapeutic target. Clin Breast Cancer. 2013; 13(1): 7-15. DOI: https://doi.org/10.1016/j.clbc.2012.09.017

Yun CW and Lee SH. The roles of autophagy in cancer. Int J Mol Sci. 2018; 19(11): 3466. DOI: https://doi.org/10.3390/ijms19113466

Mauthe M, Orhon I, Rocchi C, Zhou X, Luhr M, Hijlkema KJ, et al. Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion. Autophagy. 2018; 14(8): 1435-1455. DOI: https://doi.org/10.1080/15548627.2018.1474314

Kocak M, Ezazi Erdi S, Jorba G, Maestro I, Farrés J, Kirkin V, et al. Targeting autophagy in disease: Established and new strategies. Autophagy. 2022; 18(3): 473-495. DOI: https://doi.org/10.1080/15548627.2021.1936359