The hepatitis B virus X protein promotes hepatocellular carcinoma metastasis by upregulation of matrix metalloproteinases.
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.
Ou
Di-Peng
DP
Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Tao
Yi-Ming
YM
Tang
Fa-Qing
FQ
Yang
Lian-Yue
LY
D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000556:secondary*; D002465:Cell Movement; D006801:Humans; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology*; D053511:Matrix Metalloproteinase 14 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins
D012333:RNA, Messenger; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D020778:Matrix Metalloproteinase 2; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14