The hepatitis B virus X protein promotes hepatocellular carcinoma metastasis by upregulation of matrix metalloproteinases
| Autor: | Lian-Yue Yang, Fa-Qing Tang, Yi-Ming Tao, Di-Peng Ou |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Carcinoma Hepatocellular viruses Matrix metalloproteinase medicine.disease_cause Orthohepadnavirus Downregulation and upregulation Cell Movement Matrix Metalloproteinase 14 medicine Humans Viral Regulatory and Accessory Proteins RNA Messenger Hepatitis B virus biology Liver Neoplasms Prognosis biology.organism_classification medicine.disease digestive system diseases Up-Regulation HBx Liver Oncology Hepadnaviridae Hepatocellular carcinoma Trans-Activators Cancer research Matrix Metalloproteinase 2 Liver cancer |
| Zdroj: | International Journal of Cancer. 120:1208-1214 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.22452 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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