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

被引：109
作者：
Hsieh, Antony [1 ]
Kim, Hyeon-Seop [1 ]
Lim, Seung-Oe [1 ]
Yu, Dae-Yeul [2 ]
Jung, Guhung [1 ]
机构：
[1] Seoul Natl Univ, Dept Biol Sci, Coll Nat Sci, Seoul 151742, South Korea
[2] Korea Res Inst Biosci & Biotechnol, Anim Mol Physiol Res Unit, Taejon, South Korea
来源：
CANCER LETTERS | 2011年 / 300卷 / 02期
关键词：
Hepatitis B virus; Hepatitis B viral X protein; Adenomatous polyposis coli; Wnt; beta Catenin; Hepatocellular carcinoma; NF-KAPPA-B; HEPATOCELLULAR-CARCINOMA; BETA-CATENIN; HBX PROTEIN; C-MYC; MUTATIONS; GENE; APC; CANCER; INDUCTION;
D O I：
10.1016/j.canlet.2010.09.018
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
HBV X protein is a transactivator of several cellular signaling pathways including Wnt which contributes to HBV associated neoplasia The Wnt/beta-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 beta-catenin from its degradation complex This results in beta-catenin upregulation in the nucleus and the activation of Wnt signaling We show that Wnt inhibitors curcumin and quercetin target downstream beta-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 (C) 2010 Elsevier Ireland Ltd All rights reserved
引用
收藏
页码：162 / 172
页数：11
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