The Roles of Autophagy in Cancer

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2018 Nov 8

PMID 30400561

Citations 422

Authors

Chul Won Yun

Sang Hun Lee

Affiliations

Soon will be listed here.

Abstract

Autophagy is an intracellular degradative process that occurs under several stressful conditions, including organelle damage, the presence of abnormal proteins, and nutrient deprivation. The mechanism of autophagy initiates the formation of autophagosomes that capture degraded components and then fuse with lysosomes to recycle these components. The modulation of autophagy plays dual roles in tumor suppression and promotion in many cancers. In addition, autophagy regulates the properties of cancer stem-cells by contributing to the maintenance of stemness, the induction of recurrence, and the development of resistance to anticancer reagents. Although some autophagy modulators, such as rapamycin and chloroquine, are used to regulate autophagy in anticancer therapy, since this process also plays roles in both tumor suppression and promotion, the precise mechanism of autophagy in cancer requires further study. In this review, we will summarize the mechanism of autophagy under stressful conditions and its roles in tumor suppression and promotion in cancer and in cancer stem-cells. Furthermore, we discuss how autophagy is a promising potential therapeutic target in cancer treatment.

Citing Articles

The RNA-binding protein ELAVL1 promotes Beclin1-mediated cellular autophagy and thus endometrial cancer development by affecting LncRNA-neat stability.

Luo Y, Zhong X, Sun X, Fan J Cancer Biol Ther. 2025; 26(1):2469927.

PMID: 40018990 PMC: 11875488. DOI: 10.1080/15384047.2025.2469927.

Autophagy and Cancer: Insights into Molecular Mechanisms and Therapeutic Approaches for Chronic Myeloid Leukemia.

Kausar M, Anwar S, Khan Y, Saleh A, Ahmed M, Kaur S Biomolecules. 2025; 15(2).

PMID: 40001518 PMC: 11853340. DOI: 10.3390/biom15020215.

Caspase 3 and caspase 7 promote cytoprotective autophagy and the DNA damage response during non-lethal stress conditions in human breast cancer cells.

Samarasekera G, Go N, Choutka C, Xu J, Takemon Y, Chan J PLoS Biol. 2025; 23(3):e3003034.

PMID: 39982959 PMC: 11882052. DOI: 10.1371/journal.pbio.3003034.

Simultaneous effect of miR-21 suppression and miR-143 restoration on inhibition of proliferation and migration in SW-480 colorectal cancer cells.

Tohidast M, Amini M, Doustvandi M, Hosseini S, Bilan F, Mozammel N Bioimpacts. 2025; 15:30255.

PMID: 39963562 PMC: 11830141. DOI: 10.34172/bi.30255.

Chronotype and Cancer: Emerging Relation Between Chrononutrition and Oncology from Human Studies.

Godos J, Currenti W, Ferri R, Lanza G, Caraci F, Frias-Toral E Nutrients. 2025; 17(3).

PMID: 39940387 PMC: 11819666. DOI: 10.3390/nu17030529.

References

Vaupel P, Mayer A . Hypoxia and anemia: effects on tumor biology and treatment resistance. Transfus Clin Biol. 2005; 12(1):5-10. DOI: 10.1016/j.tracli.2004.11.005. View

Gupta P, Chaffer C, Weinberg R . Cancer stem cells: mirage or reality?. Nat Med. 2009; 15(9):1010-2. DOI: 10.1038/nm0909-1010. View

Ktistakis N, Tooze S . Digesting the Expanding Mechanisms of Autophagy. Trends Cell Biol. 2016; 26(8):624-635. DOI: 10.1016/j.tcb.2016.03.006. View

Moloney J, Cotter T . ROS signalling in the biology of cancer. Semin Cell Dev Biol. 2017; 80:50-64. DOI: 10.1016/j.semcdb.2017.05.023. View

Komatsu M, Waguri S, Ueno T, Iwata J, Murata S, Tanida I . Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J Cell Biol. 2005; 169(3):425-34. PMC: 2171928. DOI: 10.1083/jcb.200412022. View

Scott R, Schuldiner O, Neufeld T . Role and regulation of starvation-induced autophagy in the Drosophila fat body. Dev Cell. 2004; 7(2):167-78. DOI: 10.1016/j.devcel.2004.07.009. View

Ronan B, Flamand O, Vescovi L, Dureuil C, Durand L, Fassy F . A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy. Nat Chem Biol. 2014; 10(12):1013-9. DOI: 10.1038/nchembio.1681. View

Thurston T, Boyle K, Allen M, Ravenhill B, Karpiyevich M, Bloor S . Recruitment of TBK1 to cytosol-invading Salmonella induces WIPI2-dependent antibacterial autophagy. EMBO J. 2016; 35(16):1779-92. PMC: 5010046. DOI: 10.15252/embj.201694491. View

Yu L, Chen Y, Tooze S . Autophagy pathway: Cellular and molecular mechanisms. Autophagy. 2017; 14(2):207-215. PMC: 5902171. DOI: 10.1080/15548627.2017.1378838. View

10.

Njaria P, Okombo J, Njuguna N, Chibale K . Chloroquine-containing compounds: a patent review (2010 - 2014). Expert Opin Ther Pat. 2015; 25(9):1003-24. PMC: 7103710. DOI: 10.1517/13543776.2015.1050791. View

11.

Hashimoto I, Koizumi K, Tatematsu M, Minami T, Cho S, Takeno N . Blocking on the CXCR4/mTOR signalling pathway induces the anti-metastatic properties and autophagic cell death in peritoneal disseminated gastric cancer cells. Eur J Cancer. 2008; 44(7):1022-9. DOI: 10.1016/j.ejca.2008.02.043. View

12.

Jin F, Wang Y, Li M, Zhu Y, Liang H, Wang C . MiR-26 enhances chemosensitivity and promotes apoptosis of hepatocellular carcinoma cells through inhibiting autophagy. Cell Death Dis. 2017; 8(1):e2540. PMC: 5386370. DOI: 10.1038/cddis.2016.461. View

13.

Sou Y, Waguri S, Iwata J, Ueno T, Fujimura T, Hara T . The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in mice. Mol Biol Cell. 2008; 19(11):4762-75. PMC: 2575156. DOI: 10.1091/mbc.e08-03-0309. View

14.

Guo J, White E . Autophagy is required for mitochondrial function, lipid metabolism, growth, and fate of KRAS(G12D)-driven lung tumors. Autophagy. 2013; 9(10):1636-8. PMC: 5424446. DOI: 10.4161/auto.26123. View

15.

Wang J, Wu G . Role of autophagy in cisplatin resistance in ovarian cancer cells. J Biol Chem. 2014; 289(24):17163-73. PMC: 4059157. DOI: 10.1074/jbc.M114.558288. View

16.

Phadwal K, Watson A, Simon A . Tightrope act: autophagy in stem cell renewal, differentiation, proliferation, and aging. Cell Mol Life Sci. 2012; 70(1):89-103. PMC: 3535400. DOI: 10.1007/s00018-012-1032-3. View

17.

Torii S, Yoshida T, Arakawa S, Honda S, Nakanishi A, Shimizu S . Identification of PPM1D as an essential Ulk1 phosphatase for genotoxic stress-induced autophagy. EMBO Rep. 2016; 17(11):1552-1564. PMC: 5090708. DOI: 10.15252/embr.201642565. View

18.

Mukhopadhyay S, Panda P, Sinha N, Das D, Bhutia S . Autophagy and apoptosis: where do they meet?. Apoptosis. 2014; 19(4):555-66. DOI: 10.1007/s10495-014-0967-2. View

19.

Liang D, El-Zein R, Dave B . Autophagy Inhibition to Increase Radiosensitization in Breast Cancer. J Nucl Med Radiat Ther. 2015; 6(5). PMC: 4657142. DOI: 10.4172/2155-9619.1000254. View

20.

Masliah-Planchon J, Garinet S, Pasmant E . RAS-MAPK pathway epigenetic activation in cancer: miRNAs in action. Oncotarget. 2015; 7(25):38892-38907. PMC: 5122439. DOI: 10.18632/oncotarget.6476. View