Pre-s2 mutant-induced mammalian target of rapamycin signal pathways as potential therapeutic targets for hepatitis B virus-associated hepatocellular carcinoma

Chiao Fang Teng, Han Chieh Wu, Woei Cherng Shyu, Long Bin Jeng, Ih Jen Su*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

23 Scopus citations

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 languageEnglish
Pages (from-to)429-438
Number of pages10
JournalCell Transplantation
Volume26
Issue number3
DOIs
StatePublished - 2017
Externally publishedYes

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

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