Pre-S2 and HBV associated hepatocellular carcinoma

Abstract

Hepatitis B virus (HBV) infection is a primary cause of hepatocellular carcinoma (HCC). Under selection pressures of host immunity and/or immunoprophylaxis and antiviral therapies, HBV evolves by accumulating mutations in its genome. Several studies highlighted the considerable importance of HBV surface (HBs) protein mutants (pre-S/S variants) in tumorigenesis. Among those mutants, pre-S2 mutants have been recognized as "precursor lesions of HCC" and as risk factors for post-operative recurrence of HCC. Pre-S2 mutants play important roles in tumor progression and induce various mechanisms of tumorigenesis. These roles include that the cytoplasmic orientation of the pre-S2 domain is essential for the transcriptional activator C-terminally truncated middle surface protein (MHBst) which participates in the development of hepatocellular carcinoma. Pre-S2 mutants may also play important roles in HBV tumorigenesis by inducing both endoplasmic reticulum stress-dependent and endoplasmic reticulum (ER) stress-independent pathways. Because HCC has poor prognosis and its incidence is increasing, methods for the prevention and treatment of HCC should be comprehensive. Emerging treatments based on ER stress may provide a new strategy.

Keywords

Pre-S2 / hepatocellular carcinoma / hepatitis B virus / endoplasmic reticulum stress

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