IGF-II induced by hepatitis B virus X protein regulates EMT via SUMO mediated loss of E- cadherin in mice

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Title
IGF-II induced by hepatitis B virus X protein regulates EMT via SUMO mediated loss of E- cadherin in mice
Author(s)
Hye-Lin Ha; Taeho Kwon; In Seon Bak; R L Erikson; Bo Yeon Kim; Dae Yeul Yu
Bibliographic Citation
Oncotarget, vol. 7, no. 35, pp. 56944-56957
Publication Year
2016
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer mortality. Prognosis of this disease largely depends on its stage. An Enlarged liver, due to dysplasia, may be a critical point in the multi-step progression to HCC. The mechanism underlying hepatomegaly in human and mouse models are poorly understood. We previously reported we observed enlarged liver in hepatitis B virus X protein (HBx) expressing mice (HBx mice). Here we identify the critical role of HBx induced IGF-II in hepatomegaly in mice and abnormal cell growth in human hepatoma cells. We found that HBx induced IGF-II is essential to induce epithelial-mesenchymal transition (EMT) through loss of E-cadherin. In mouse liver, loss of E-cadherin was mediated by post-translational regulation, at least in part, by protease and SUMOylation not by transcriptional regulation. In contrast, in hepatoma cell line (HepG2 cells) Akt signal pathway controls the mRNA expression level of EMT-related transcription factors, especially Twist, in addition to post- translational modification through SUMOylation. Thus, IGF-II-mediated loss of E-cadherin is central in developing hepatomegaly in mice and abnormal cell growth in the hepatoma cell line. HBx induced IGF-II represents a potential biomarker, which is also a therapeutic target in HCC.
Keyword
Epithelial-mesenchymal transitionHepatitis B virus X proteinHepatocellular carcinomaIGF-IISUMOylation
ISSN
1949-2553
Publisher
Impact Journals
DOI
http://dx.doi.org/10.18632/oncotarget.10922
Type
Article
Appears in Collections:
Jeonbuk Branch Institute > Primate Resources Center > 1. Journal Articles
Ochang Branch Institute > Anticancer Agent Research Center > 1. Journal Articles
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