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 MAPK 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 TSP-1 overexpression. Furthermore, the MAPK signaling pathway is predominantly responsible for HGF-induced TSP-1 downregulation. We conclude that HGF is a potential downregulator of TSP-1, through MAPK 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.
Wei
Wei
W
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Ji'nan 250012, Shandong, China.
Kong
Beihua
B
Yang
Qifeng
Q
Qu
Xun
X
D000230:Adenocarcinoma / Q000473:pathology*; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D019700:Thrombospondin 1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D002070:Butadienes; C066855:HGF protein, human; D009363:Neoplasm Proteins; D009570:Nitriles; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D019700:Thrombospondin 1; C113580:U 0126; D017228:Hepatocyte Growth Factor; D020780:Matrix Metalloproteinase 9