Both focal adhesion kinase and c-Ras are required for the enhanced matrix metalloproteinase 9 secretion by fibronectin in ovarian cancer cells.
Cell adhesion to the extracellular matrix appears to trigger a cascade of intracellular signalings. We have shown previously that treatment of ovarian cancer cells with peritoneal conditioned medium or purified fibronectin (FN) activated matrix metalloproteinase 9 secretion and, thereby, cancer cell invasion. By use of antisense oligonucleotides to focal adhesion kinase (FAK) and a dominant-negative mutant of ras (S17Nras), we found that both FAK and c-Ras were required for the activation of matrix metalloproteinase 9 secretion by FN. In addition, both antisense oligonucleotides to FAK and S17Nras inhibited mitogen-activated protein kinase activation by FN treatment, suggesting the involvement of mitogen-activated protein kinase in the FN-dependent signaling.
Shibata
K
K
Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Japan.
Kikkawa
F
F
Nawa
A
A
Thant
A A
AA
Naruse
K
K
Mizutani
S
S
Hamaguchi
M
M
D015815:Cell Adhesion Molecules / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000494:pharmacology*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D011905:Genes, ras; D006801:Humans; D020780:Matrix Metalloproteinase 9; D016376:Oligonucleotides, Antisense; D010051:Ovarian Neoplasms / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D005353:Fibronectins; D016376:Oligonucleotides, Antisense; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; D018631:ras Proteins