Hepatitis B viral X protein interacts with tumor suppressor adenomatous polyposis coli to activate Wnt/β-catenin signaling

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Title
Hepatitis B viral X protein interacts with tumor suppressor adenomatous polyposis coli to activate Wnt/β-catenin signaling
Author(s)
A Hsieh; H S Kim; S O Lim; Dae Yeul Yu; G Jung
Bibliographic Citation
Cancer Letters, vol. 300, no. 2, pp. 162-172
Publication Year
2011
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.
Keyword
β-CateninAdenomatous polyposis coliHepatitis B viral X proteinHepatitis B virusHepatocellular carcinomaWnt
ISSN
0304-3835
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.canlet.2010.09.018
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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