Pre-S2 Mutant-Induced Mammalian Target of Rapamycin Signal Pathways as Potential Therapeutic Targets for Hepatitis B Virus-Associated Hepatocellular Carcinoma

Cell Transplantation

Review

Woei-Cherng Shyu¹  Han-Chieh Wu²  Ih-Jen Su³  Chiao-Fang Teng⁴  Long-Bin Jeng⁴ 

[1] Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan;Graduate Institute of Immunology, China Medical University, Taichung, Taiwan;National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan;National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan;Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan;Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan;Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan;

关键词: Hepatitis B virus (HBV);    Hepatocellular carcinoma (HCC);    Ground glass hepatocytes (GGHs);    Pre-S2 mutant;    Mammalian target of rapamycin (mTOR);   

DOI  :  10.3727/096368916X694382

 received in 2016-08-31, accepted in 2017-01-06,  发布年份 2017

来源: Sage Journals

【 摘 要 】

Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Pre-S2 mutant represents an HBV oncoprotein that is accumulated in the endoplasmic reticulum (ER) and manifests as type II ground glass hepatocytes (GGHs). Pre-S2 mutant can induce ER stress and initiate multiple ER stress-dependent or -independent cellular signal pathways, leading to growth advantage of type II GGH. Importantly, the mammalian target of rapamycin (mTOR) signal pathways are consistently activated throughout the liver tumorigenesis in pre-S2 mutant transgenic mice and in human HCC tissues, leading to hepatocyte proliferation, metabolic disorders, and HCC tumorigenesis. In this review, we summarize the pre-S2 mutant-induced mTOR signal pathways and its implications in HBV-related HCC tumorigenesis. Clinically, the presence of pre-S2 mutant exhibits a high resistance to antiviral treatment and carries a high risk of HCC development in patients with chronic HBV infection. Targeting at pre-S2 mutant-induced mTOR signal pathways may thus provide potential strategies for the prevention or therapy of HBV-associated HCC.

【 授权许可】

Unknown   
© 2017 SAGE Publications Inc

【 图 表 】

Figure 2.