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Cancer Cell Biology
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The hepatitis B virus X protein promotes hepatocellular carcinoma metastasis by upregulation of matrix metalloproteinases
Article first published online: 22 DEC 2006
DOI: 10.1002/ijc.22452
Copyright © 2006 Wiley-Liss, Inc.
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How to Cite
Ou, D.-P., Tao, Y.-M., Tang, F.-Q. and Yang, L.-Y. (2007), The hepatitis B virus X protein promotes hepatocellular carcinoma metastasis by upregulation of matrix metalloproteinases. Int. J. Cancer, 120: 1208–1214. doi: 10.1002/ijc.22452
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Publication History
- Issue published online: 30 JAN 2007
- Article first published online: 22 DEC 2006
- Manuscript Accepted: 10 OCT 2006
- Manuscript Received: 18 JUL 2006
Funded by
- National Natural Science Foundation of China. Grant Number: 30371595
- National Key Technologies R&D Program. Grant Number: 2001BA703B04
- China Basic Research Program. Grant Number: 2004CB720303
- Specialized Research Fund for Doctoral Program of Higher Education. Grant Number: 20030533037
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Keywords:
- HBx;
- HCC;
- MT1-MMP;
- invasion and metastasis;
- signal transduction pathway
Abstract
The hepatitis B virus (HBV) is a major cause of human hepatocellular carcinoma (HCC) which has a very high mortality rate due to high incidence of metastasis. It is unknown whether HBV contributes to HCC metastasis. In this report, we present clinical data obtained from HCC patients indicating that the expression of hepatitis B virus X protein (HBx) in HCC is associated with an increased expression of membrane-type 1 matrix metalloproteinase (MT1-MMP), and matrix metalloproteinase-2(MMP-2), which correlates with a poor prognosis. We further demonstrate experimentally that HBx upregulates MT1-MMP, which in turn induces MMP-2. Significantly, HBx-mediated MMP activation is associated with a marked increase of cell migration, as revealed by both wound-healing and transwell migration assays, suggesting that HBx may facilitate tumor cell invasion by upregulation of MMPs and subsequent destruction of the extracellular matrix. Together, our results support a model in which HBx contributes to HCC metastasis by upregulation of MMPs. © 2006 Wiley-Liss, Inc.