Hepatocyte growth factor enhances ovarian cancer cell invasion through downregulation of thrombospondin-1

Hepatocyte growth factor (HGF) plays an important role in stimulating tumor invasion and metastasis of tumor cells. However, the exact mechanisms of HGF regulation of cell invasion are largely unknown. In this study, we demonstrated that the MAPAPK specific inhibitor U0126 prevented the HGF-induced invasion of SKOV-3 cells. HGF stimulation of cell invasion and enhancement of MMP-9 expression were partially suppressed by TSPSP-1 overexpression. Furthermore, the MAPAPK signaling pathway is predominantly responsible for HGF-induced TSPSP-1 downregulation. We conclude that HGF is a potential downregulator of TSPSP-1, through MAPAPK signaling pathways, leading to the induction of MMP-9 expression and subsequent invasion of SKOV-3 cells. This study enhances our understanding of the mechanisms of signaling transduction in the HGF-induced invasion and progression of ovarian cancer.