Abstract
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.
Original language | English |
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Pages (from-to) | 429-438 |
Number of pages | 10 |
Journal | Cell Transplantation |
Volume | 26 |
Issue number | 3 |
DOIs | |
State | Published - 2017 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2017 Cognizant, LLC.
Keywords
- Ground glass hepatocytes (GGHs)
- Hepatitis B virus (HBV)
- Hepatocellular carcinoma (HCC)
- Mammalian target of rapamycin (mTOR)
- Pre-S2 mutant