The Role of Autophagy in Gastric Cancer Chemoresistance: Friend or Foe?

Jing-Li Xu,Xiang-Dong Cheng,Han-Dong Xu,Jiang-Jiang Qin,Yan-Cheng Tang,Li Yuan,Zhi-Yuan Xu

doi:10.3389/fcell.2020.621428

Abstract

Gastric cancer is the third most common cause of cancer-related death worldwide. Drug resistance is the main inevitable and vital factor leading to a low 5-year survival rate for patients with gastric cancer. Autophagy, as a highly conserved homeostatic pathway, is mainly regulated by different proteins and non-coding RNAs (ncRNAs) and plays dual roles in drug resistance of gastric cancer. Thus, targeting key regulatory nodes in the process of autophagy by small molecule inhibitors or activators has become one of the most promising strategies for the treatment of gastric cancer in recent years. In this review, we provide a systematic summary focusing on the relationship between autophagy and chemotherapy resistance in gastric cancer. We comprehensively discuss the roles and molecular mechanisms of multiple proteins and the emerging ncRNAs including miRNAs and lncRNAs in the regulation of autophagy pathways and gastric cancer chemoresistance. We also summarize the regulatory effects of autophagy inhibitor and activators on gastric cancer chemoresistance. Understanding the vital roles of autophagy in gastric cancer chemoresistance will provide novel opportunities to develop promising therapeutic strategies for gastric cancer.

Highlights

Gastric cancer is one of the most common gastrointestinal tumors in the world, with more than one million new cases every year, and remains the third leading cause of cancer-related deaths (Fitzmaurice et al, 2019; Thrift and El-Serag, 2019)
The specific roles of autophagy in tumors depend on tumor type and tumor heterogeneity, which is regulated by multiple proteins and non-coding RNAs (Jiang et al, 2020; Perez-Montoyo, 2020)
Tian et al (2018) have suggested that miR-361-5p negatively regulates the expression of FOXM1, which further causes an increase in the expression of p-AKT and Mammalian target of rapamycin (mTOR), the inhibition of autophagy, and the enhanced sensitivity of gastric cancer cells to Docetaxel (DOC) in vitro

Summary

Introduction

Gastric cancer is one of the most common gastrointestinal tumors in the world, with more than one million new cases every year, and remains the third leading cause of cancer-related deaths (Fitzmaurice et al, 2019; Thrift and El-Serag, 2019). Further studies have shown that CD133 can increase autophagy and the stemness of gastric cancer cells via activating the PI3K/AKT/mTOR signaling pathway, causing DDP resistance of gastric cancer cells in vivo and in vitro (Lu et al, 2019).

Results

Conclusion