Phosphatidylinositol 3-kinase activity in epidermal growth factor-stimulated matrix metalloproteinase-9 production and cell surface association.

摘要: Activation of the epidermal growth factor (EGF) receptor regulates many processes associated with metastasis, including modulation cell:cell and cell:substrate interactions, production matrix-degrading proteinases, cellular migration. We have demonstrated previously that EGF stimulates migration matrix metalloproteinase (MMP)-9-dependent invasion ovarian cancer cells. In this study, we compare roles EGF-induced phosphatidylinositol 3-kinase (PI3K) mitogen-activated protein kinase (MAPK) activities in regulation responses tumor cell metastasis. Inhibition PI3K MAPK activity impairs EGF-stimulated migration, vitro invasion, MMP-9 production. is not required for disruption junctions, whereas inhibitors extracellular signal-regulated (ERK)1/ERK2 activation p38 block EGF-dependent junction dissolution. promotes pro-MMP-9 binding to surface through a mechanism independent enzyme concentration. Interestingly, inhibition abolishes association pro-MMP-9, MAPKs only partially response. These data suggest PI3K-dependent induction component may facilitate gelatinase-mediated supports an expanded role elevated addition, our findings support hypothesis divergent regulate distinct events factor-induced