The role of autophagy in hepatocellular carcinoma: friend or foe.

Lian Liu,Pei-Yuan Li,Jia-Zhi Liao,Xing-Xing He

doi:10.18632/oncotarget.17202

Abstract

Autophagy is an evolutionarily conserved lysosome-dependent catabolic process which degrades cell’s components in order to recycle substrates to exert optimally and adapt to tough circumstances. It is a critical cellular homeostatic mechanism with stress resistance, immunity, antiaging, and pro-tumor or anti-tumor effects. Among these, the role of autophagy in cancer is the most eye-catching that is not immutable but dynamic and highly complex. Basal autophagy acts as a tumor suppressor by maintaining genomic stability in normal cells. However, once a tumor is established, unbalanced autophagy will contribute to carcinoma cell survival under tumor microenvironment and in turn promote tumor growth and development. The dynamic role of autophagy can also apply on hepatocellular carcinoma (HCC). HCC is a highly malignant cancer with high morbidity and poor survival rate. Decline or overexpression of autophagic essential genes such as ATG7, ATG5 or Beclin 1 plays a key role in the occurrence and development of HCC but the exact mechanisms are still highly controversial. Signaling pathways or molecules involving in autophagy, for example PI3K/AKT/mTOR pathway, ERK/MAPK pathway, PERK pathway, p53, LncRNA PTENP1 (Long non-coding RNA PTENP1), microRNA-375 and so on, occupy an important position in the complex role of autophagy in HCC. Here, we discuss the dynamic role, the signaling pathways and the potential prognostic and therapy value of autophagy in HCC.

Highlights

Since Christian de Duve proposed the term ‘autophagy’, which he introduced at the CIBA Foundation Symposium on Lysosomes in 1963 [1], growing enthusiasm has done much to the discovery of characteristics and functions of autophagy
It suggests that blocking of Phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (AKT)/mTOR signaling can induce the occurrence of autophagy and contribute to the suppression of hepatocellular carcinoma (HCC). All these lines of evidence suggest that suppression of PI3K/AKT/mTOR signaling pathway induces the initiation of autophagy, and inhibits the proliferation and migration of HCC cells
Autophagy plays an anti-tumor role in normal liver cells by maintaining cell homeostasis, www.impactjournals.com/oncotarget but once the tumor is formed, it promotes the survival of HCC cells under tumor microenvironment

Summary

Introduction

Since Christian de Duve proposed the term ‘autophagy’, which he introduced at the CIBA Foundation Symposium on Lysosomes in 1963 [1], growing enthusiasm has done much to the discovery of characteristics and functions of autophagy. Autophagy encourages the development of liver cancer via inhibiting the expression of tumor suppressors or contributing to the chemoresistance of HCC cells.

Results

Conclusion