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World J Gastroenterol. Nov 7, 2018; 24(41): 4643-4651
Published online Nov 7, 2018. doi: 10.3748/wjg.v24.i41.4643
Role of autophagy in tumorigenesis, metastasis, targeted therapy and drug resistance of hepatocellular carcinoma
Fang Huang, Bing-Rong Wang, Yi-Gang Wang
Fang Huang, Yi-Gang Wang, Department of Pathology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
Bing-Rong Wang, Yi-Gang Wang, Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
Author contributions: Huang F, Wang BR and Wang YG performed the literature review and drafted the manuscript; Huang F and Wang YG revised the manuscript; All the authors read and approved the final version to be published.
Supported by Natural Science Foundation of China, No. 81803069; Natural Science Foundation of Zhejiang Province of China, No. LY18C070002 and No. LY16H160056;and 521 Talent Project of Zhejiang Sci-Tech University.
Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yi-Gang Wang, PhD, Associate Professor, Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, No. 5, Road 2, Xiasha District, Hangzhou 310018, Zhejiang Province, China. wangyigang43@163.com
Telephone: +86-571-86843187 Fax: +86-571-86843185
Received: July 5, 2018
Peer-review started: July 5, 2018
First decision: August 25, 2018
Revised: September 4, 2018
Accepted: October 5, 2018
Article in press: October 5, 2018
Published online: November 7, 2018
Abstract

Autophagy is a “self-degradative” process and is involved in the maintenance of cellular homeostasis and the control of cellular components by facilitating the clearance or turnover of long-lived or misfolded proteins, protein aggregates, and damaged organelles. Autophagy plays a dual role in cancer, including in tumor progression and tumor promotion, suggesting that autophagy acts as a double-edged sword in cancer cells. Liver cancer is one of the greatest leading causes of cancer death worldwide due to its high recurrence rate and poor prognosis. Especially in China, liver cancer has become one of the most common cancers due to the high infection rate of hepatitis virus. In primary liver cancer, hepatocellular carcinoma (HCC) is the most common type. Considering the perniciousness and complexity of HCC, it is essential to elucidate the function of autophagy in HCC. In this review, we summarize the physiological function of autophagy in cancer, analyze the role of autophagy in tumorigenesis and metastasis, discuss the therapeutic strategies targeting autophagy and the mechanisms of drug-resistance in HCC, and provide potential methods to circumvent resistance and combined anticancer strategies for HCC patients.

Keywords: Autophagy, Drug resistance, Hepatocellular carcinoma, Tumorigenesis, Metastasis, Targeted therapy

Core tip: Liver cancer seriously threatens human health, due to its high recurrence rate and poor prognosis. Hepatocellular carcinoma is the most common type of primary liver cancer. Autophagy plays a dual role in cancer. Basic autophagy exerts a tumor suppression function by maintaining genomic stability in normal cells. When cancer occurs, activated autophagy benefits cancer cell survival and promotes cancer development. However, the mechanism and function of autophagy in human cancers, especially liver cancer, have not been clarified. We summarize the physiological function of autophagy and its role in tumorigenesis, metastasis, targeted therapy and drug-resistance in hepatocellular carcinoma.