Autophagy Takes Center Stage As a Possible Cancer Hallmark

Overview

Journal Front Oncol

Specialty Oncology

Date 2020 Nov 16

PMID 33194736

Citations 25

Authors

Jose G Alvarez-Meythaler

Yoelsis Garcia-Mayea

Cristina Mir

Hiroshi Kondoh

Matilde E LLeonart

Affiliations

Soon will be listed here.

Abstract

Cancer remains one of the leading causes of death worldwide, despite significant advances in cancer research and improvements in anticancer therapies. One of the major obstacles to curing cancer is the difficulty of achieving the complete annihilation of resistant cancer cells. The resistance of cancer cells may not only be due to intrinsic factors or factors acquired during the evolution of the tumor but may also be caused by chemotherapeutic treatment failure. Conversely, autophagy is a conserved cellular process in which intracellular components, such as damaged organelles, aggregated or misfolded proteins and macromolecules, are degraded or recycled to maintain cellular homeostasis. Importantly, autophagy is an essential mechanism that plays a key role in tumor initiation and progression. Depending on the cellular context and microenvironmental conditions, autophagy acts as a double-edged sword, playing a role in inducing apoptosis or promoting cell survival. In this review, we propose several scenarios in which autophagy could contribute to cell survival or cell death. Moreover, a special focus on novel promising targets and therapeutic strategies based on autophagic resistant cells is presented.

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References

Gudipaty S, Conner C, Rosenblatt J, Montell D . Unconventional Ways to Live and Die: Cell Death and Survival in Development, Homeostasis, and Disease. Annu Rev Cell Dev Biol. 2018; 34:311-332. PMC: 6791364. DOI: 10.1146/annurev-cellbio-100616-060748. View

Kiraz Y, Adan A, Yandim M, Baran Y . Major apoptotic mechanisms and genes involved in apoptosis. Tumour Biol. 2016; 37(7):8471-86. DOI: 10.1007/s13277-016-5035-9. View

Han H, Li J, Feng X, Zhou H, Guo S, Zhou W . Autophagy-related genes are induced by histone deacetylase inhibitor suberoylanilide hydroxamic acid via the activation of cathepsin B in human breast cancer cells. Oncotarget. 2017; 8(32):53352-53365. PMC: 5581115. DOI: 10.18632/oncotarget.18410. View

Rosenfeld M, Ye X, Supko J, Desideri S, Grossman S, Brem S . A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme. Autophagy. 2014; 10(8):1359-68. PMC: 4203513. DOI: 10.4161/auto.28984. View

Seo J, Seong D, Nam Y, Hwang C, Lee S, Lee C . Beclin 1 functions as a negative modulator of MLKL oligomerisation by integrating into the necrosome complex. Cell Death Differ. 2020; 27(11):3065-3081. PMC: 7560833. DOI: 10.1038/s41418-020-0561-9. View

Liu H, Du Y, Zhang Z, Lv L, Xiong W, Zhang L . Autophagy contributes to hypoxia-induced epithelial to mesenchymal transition of endometrial epithelial cells in endometriosis. Biol Reprod. 2018; 99(5):968-981. PMC: 6297317. DOI: 10.1093/biolre/ioy128. View

Sotelo J, Briceno E, Lopez-Gonzalez M . Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2006; 144(5):337-43. DOI: 10.7326/0003-4819-144-5-200603070-00008. View

Kim T, Lee S, Kim M, Cheon C, Ko S . Kaempferol induces autophagic cell death via IRE1-JNK-CHOP pathway and inhibition of G9a in gastric cancer cells. Cell Death Dis. 2018; 9(9):875. PMC: 6115440. DOI: 10.1038/s41419-018-0930-1. View

Polivka Jr J, Janku F . Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway. Pharmacol Ther. 2013; 142(2):164-75. DOI: 10.1016/j.pharmthera.2013.12.004. View

10.

Xiong H, Ni Z, Jiang S, Li X, He J, Gong W . LncRNA HULC triggers autophagy via stabilizing Sirt1 and attenuates the chemosensitivity of HCC cells. Oncogene. 2017; 36(25):3528-3540. DOI: 10.1038/onc.2016.521. View

11.

Chen C, Tseng Y, Wu J, Chen G, Lin K, Hwang S . Suppression of hepatocellular carcinoma by baculovirus-mediated expression of long non-coding RNA PTENP1 and MicroRNA regulation. Biomaterials. 2015; 44:71-81. DOI: 10.1016/j.biomaterials.2014.12.023. View

12.

Lv W, Sui L, Yan X, Xie H, Jiang L, Geng C . ROS-dependent Atg4 upregulation mediated autophagy plays an important role in Cd-induced proliferation and invasion in A549 cells. Chem Biol Interact. 2017; 279:136-144. DOI: 10.1016/j.cbi.2017.11.013. View

13.

Xu X, Lai Y, Hua Z . Apoptosis and apoptotic body: disease message and therapeutic target potentials. Biosci Rep. 2018; 39(1). PMC: 6340950. DOI: 10.1042/BSR20180992. View

14.

Liu G, Pei F, Yang F, Li L, Amin A, Liu S . Role of Autophagy and Apoptosis in Non-Small-Cell Lung Cancer. Int J Mol Sci. 2017; 18(2). PMC: 5343902. DOI: 10.3390/ijms18020367. View

15.

Galluzzi L, Bravo-San Pedro J, Vitale I, Aaronson S, Abrams J, Adam D . Essential versus accessory aspects of cell death: recommendations of the NCCD 2015. Cell Death Differ. 2014; 22(1):58-73. PMC: 4262782. DOI: 10.1038/cdd.2014.137. View

16.

Bhat P, Kriel J, Shubha Priya B, Basappa , Shivananju N, Loos B . Modulating autophagy in cancer therapy: Advancements and challenges for cancer cell death sensitization. Biochem Pharmacol. 2017; 147:170-182. DOI: 10.1016/j.bcp.2017.11.021. View

17.

Radogna F, Dicato M, Diederich M . Cancer-type-specific crosstalk between autophagy, necroptosis and apoptosis as a pharmacological target. Biochem Pharmacol. 2015; 94(1):1-11. DOI: 10.1016/j.bcp.2014.12.018. View

18.

Wang Y, Zhang H . Regulation of Autophagy by mTOR Signaling Pathway. Adv Exp Med Biol. 2019; 1206:67-83. DOI: 10.1007/978-981-15-0602-4_3. View

19.

Zhang Y, Liu D, Hu H, Zhang P, Xie R, Cui W . HIF-1α/BNIP3 signaling pathway-induced-autophagy plays protective role during myocardial ischemia-reperfusion injury. Biomed Pharmacother. 2019; 120:109464. DOI: 10.1016/j.biopha.2019.109464. View

20.

Wei Y, Pattingre S, Sinha S, Bassik M, Levine B . JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell. 2008; 30(6):678-88. PMC: 2478643. DOI: 10.1016/j.molcel.2008.06.001. View