Hepatocyte growth factor modulates motility and invasiveness of ovarian carcinomas via ras mediated pathway.
Hepatocyte growth factor (HGF) is a multifunctional growth factor which has pleiotrophic biological effects on epitherial cells, such as proliferation, motogenesis, invasiveness and morphogenesis. Peritoneal dissemination is critical for the progression of ovarian cancer and our study revealed that HGF induces migration and invasion of ovarian cancer cells. We also demonstrated that HGF stimulates autophosphorylation of its receptor, followed by activation of the Ras-MAP (mitogen-activated peptide) kinase cascade. Moreover, infection of ovarian cancer cells with Ras dominant-negative adenovirus reduced the HGF-induced motogenic and invasive activities. Additionally, both MEK and PI3-kinase pathways downstream of Ras was involved in HGF-stimulated ovarian cancer cell invasiveness.
Ueoka
Yousuke
Y
Department of Molecular Genetics, Division of Molecular and Cell Therapeutics, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara beppu, Oita 874-0838, Japan.
Kato
Kiyoko
K
Wake
Norio
N
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D011905:Genes, ras; D017228:Hepatocyte Growth Factor / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology
D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020929:Mitogen-Activated Protein Kinase Kinases