Action and function of Wnt/β-catenin signaling in the progression from chronic hepatitis C to hepatocellular carcinoma

J Gastroenterol. 2017 Apr;52(4):419-431. doi: 10.1007/s00535-016-1299-5. Epub 2016 Dec 29.

Abstract

Hepatitis C virus (HCV) infection is one of the leading causes of hepatocellular carcinoma (HCC) worldwide but the mechanistic basis as to how chronic HCV infection furthers the HCC process remains only poorly understood. Accumulating evidence indicates that HCV core and nonstructural proteins provoke activation of the Wnt/β-catenin signaling pathway, and the evidence supporting a role of Wnt/β-catenin signaling in the onset and progression of HCC is compelling. Convincing molecular explanations as to how expression of viral effectors translates into increased activity of the Wnt/β-catenin signaling machinery are still largely lacking, hampering the design of rational strategies aimed at preventing HCC. Furthermore, how such increased signaling is especially associated with HCC oncogenesis in the context of HCV infection remains obscure as well. Here we review the body of contemporary biomedical knowledge on the role of the Wnt/β-catenin pathway in the progression from chronic hepatitis C to cirrhosis and HCC and explore potential hypotheses as to the mechanisms involved.

Keywords: Hepatitis C virus; Hepatocellular carcinoma; Wnt/β-catenin signaling.

Publication types

  • Review

MeSH terms

  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / physiopathology
  • Carcinoma, Hepatocellular / virology*
  • Cell Transformation, Neoplastic
  • Disease Progression
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / physiopathology
  • Humans
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / virology
  • Liver Neoplasms / genetics
  • Liver Neoplasms / physiopathology
  • Liver Neoplasms / virology*
  • Mutation
  • Viral Structural Proteins / physiology
  • Wnt Signaling Pathway / genetics
  • Wnt Signaling Pathway / physiology*
  • beta Catenin / genetics

Substances

  • CTNNB1 protein, human
  • Viral Structural Proteins
  • beta Catenin