Clin Exp Metastasis 2000,
PMID: 11467775
Thant, A A; Nawa, A; Kikkawa, F; Ichigotani, Y; Zhang, Y; Sein, T T; Amin, A R; Hamaguchi, M
Cell adhesion to the extracellular matrix appears to trigger a cascade of intracellular signalings. We have previously shown that treatment of ovarian cancer cells, NOM1, with fibronectin (FN) stimulated matrix metalloproteinase (MMP)-9 secretion and thereby activated the invasiveness of cells via the FAK/Ras signaling pathway. By use of chemical inhibitors, we investigated the downstream effectors critical for FN-dependent secretion of MMP-9. Treatment of cells with MEK1 inhibitors, U0126 and PD98059, dramatically suppressed the secretion of MMP-9 activated by FN. Similarly, P1-3 kinase inhibitors, Wortmannin and LY294002, strongly suppressed the FN-dependent secretion of MMP-9 together with the inhibition of Akt activation. In contrast, a specific PKC inhibitor (GF109203X) showed no inhibitory effect on the FN-dependent MMP-9 secretion. Moreover, we found that both the MEK1 inhibitor and the P13-K inhibitor, but not the PKC inhibitor, strongly suppressed the invasiveness of NOM1 cells. Taken together, our results suggest that activation of dual signaling pathways, MEKI-MAPK and P13K-Akt, is required for the FN-dependent activation of MMP-9 secretion. Our results suggest the importance of these signaling molecules as a chemotherapeutic target for cancer.
Diseases/Pathways annotated by Medline MESH: Neoplasm Invasiveness, Ovarian Neoplasms
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Text Mining Data
MMP-9 → MEKI-MAPK: "
Taken together, our results suggest that activation of dual signaling pathways,
MEKI-MAPK and P13K-Akt, is
required for the FN-dependent activation of
MMP-9 secretion
"
MMP-9 → P13K-Akt: "
Taken together, our results suggest that activation of dual signaling pathways, MEKI-MAPK and P13K-Akt , is required for the FN-dependent activation of MMP-9 secretion
"
Manually curated Databases
No curated data.