Cell Transplantation | |
Pre-S2 Mutant-Induced Mammalian Target of Rapamycin Signal Pathways as Potential Therapeutic Targets for Hepatitis B Virus-Associated Hepatocellular Carcinoma | |
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
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO202212200418927ZK.pdf | 314KB | download | |
Figure 2. | 53KB | Image | download |
【 图 表 】
Figure 2.
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