title: Action and function of Wnt/β-catenin signaling in the progression from chronic hepatitis C to hepatocellular carcinoma.
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.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, 's Gravendijkwal 230, 3015 CE, Rotterdam, Netherlands. w.wang.1@erasmusmc.nl.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, 's Gravendijkwal 230, 3015 CE, Rotterdam, Netherlands.
authors.forename: Qiuwei
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, 's Gravendijkwal 230, 3015 CE, Rotterdam, Netherlands.
authors.forename: Gwenny M
authors.initials: GM
authors.lastname: Fuhler
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, 's Gravendijkwal 230, 3015 CE, Rotterdam, Netherlands.
authors.forename: Ron
authors.initials: R
authors.lastname: Smits
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, 's Gravendijkwal 230, 3015 CE, Rotterdam, Netherlands.
authors.forename: Maikel P
authors.initials: MP
authors.lastname: Peppelenbosch
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000503:physiopathology / Q000821:virology*; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000503:physiopathology; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics / Q000503:physiopathology / Q000821:virology*; D009154:Mutation; D015678:Viral Structural Proteins / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics
chemical_list: C495270:CTNNB1 protein, human; D015678:Viral Structural Proteins; D051176:beta Catenin
keywords: Hepatitis C virus; Hepatocellular carcinoma; Wnt/β-catenin signaling