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  • Title: Hepatitis B viral X protein interacts with tumor suppressor adenomatous polyposis coli to activate Wnt/β-catenin signaling.
    Author: Hsieh A, Kim HS, Lim SO, Yu DY, Jung G.
    Journal: Cancer Lett; 2011 Jan 28; 300(2):162-72. PubMed ID: 20971552.
    Abstract:
    HBV X protein is a transactivator of several cellular signaling pathways including Wnt which contributes to HBV associated neoplasia. The Wnt/β-catenin pathway is associated with HCC-initiating cells. Here we perform a functional screen for host factors involved in the transactivational properties of HBx. We identify adenomatous polyposis coli (APC) as a binding partner of HBx and further determine that HBx competitively binds APC to displace β-catenin from its degradation complex. This results in β-catenin upregulation in the nucleus and the activation of Wnt signaling. We show that Wnt inhibitors curcumin and quercetin target downstream β-catenin activity and effectively repress HBx-mediated regulation of c-MYC and E-cadherin. Our results provide a pathological mechanism of HBx induced malignant transformation.
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