Hepatitis B virus X protein promotes cell migration by inducing matrix metalloproteinase-3

Background/Aims Hepatitis B virus (HBV), a major causative agent of hepatocellular carcinoma (HCC), encodes an oncogenic X protein (HBx) that transcriptionally activates multiple viral and cellular promoters. How this regulation influences HCC is unclear. Methods Global gene expression in HBx-expressing and non-expressing hepatoma cells was analyzed using cDNA microarrays. Results Genes that were markedly up- or down-regulated in the presence of HBx included those involved in signal transduction, metabolism, apoptosis, cytokine production, cell cycle, cell adhesion and oncogenesis. Other genes of ill-defined function were also affected. Trans-activation proficient HBx up-regulated the transcription, translation and secretion of matrix metalloproteinase-3 (MMP-3), manifest as a cell migratory phenotype. This HBx effect was abrogated in the presence of a MMP-3 specific peptide inhibitor. Conclusions HBx exerts selective transcriptional control in hepatoma cells and induces cellular migration through the activation of MMP-3.