Autophagy and liver cancer

Abstract

Autophagy is a highly conserved catabolic process that degrades cytosolic proteins and organelles via formation of autophagosomes that fuse with lysosomes to form autolysosomes, whereby autophagic cargos are degraded. Numerous studies have demonstrated that autophagy plays a critical role in the regulation of liver physiology and homeostasis, and impaired autophagy leads to the pathogenesis of various liver diseases such as viral hepatitis, alcohol associated liver diseases (AALD), non-alcoholic fatty liver diseases (NAFLD), and liver cancer. Recent evidence indicates that autophagy may play a dual role in liver cancer: inhibiting early tumor initiation while promoting progression and malignancy of already formed liver tumors. In this review, we summarized the progress of current understanding of how hepatic viral infection, alcohol consumption and diet-induced fatty liver diseases impair hepatic autophagy. We also discussed how impaired autophagy promotes liver tumorigenesis, and paradoxically how autophagy is required to promote the malignancy and progression of liver cancer. Understanding the molecular mechanisms underlying how autophagy differentially affects liver cancer development and progression may help to design better therapeutic strategies for prevention and treatment of liver cancer.

Knockdown of Atg7 suppresses Tumorigenesis in a murine model of liver cancer

“…On the contrary, autophagy contributes to survival of cancer cells by providing them with nutrients required for increased energy metabolism and removing toxic reactive oxygen radicals and mis-folded proteins [ 47 , 48 ]. Thus, inhibition of autophagy can render cancer cells susceptible to cytotoxic substances.…”

External validation of CAGE‐B and SAGE‐B scores for Asian chronic hepatitis B patients with well‐controlled viremia by antivirals

“…Primarily on the strength of antiviral treatment (AVT) using oral nucleos(t)ide analogues (NUCs) suppressing viral replication, both virological and biochemical remission could be easily achieved in most of treated patients, where necro‐inflammation and resultant fibrosis could be significantly improved 6–8 . Nevertheless, AVT decreases but does not eliminate the risk of HCC development completely, primarily owing to complex direct and indirect mechanisms of hepato‐carcinogenesis 9–13 …”

Real-Life Experience of mTOR Inhibitors in Liver Transplant Recipients in a Region Where Living Donation Is Predominant

“…mTOR inhibitors have considerable appeal in HCC patients undergoing LT, as they may prevent the proliferation of cancer cells ( Jung et al, 2018 ). Recent evidence has shown that the mTOR pathway is expressed at a higher level in HCC cells, and tumor regression was achieved in HCC-harboring animals by treatment with rapamycin ( Lee et al, 2020a ; Chao et al, 2020 ; Ferrin et al, 2020 ). Previous studies demonstrated that mTOR inhibitors may reduce the recurrence of HCC after LT ( Grigg et al, 2019 ), although most of these studies compared an mTOR inhibitor plus a low dose of TAC and a regular dose of TAC only.…”