Sustained tyrosine-phosphorylation of FAK through Rho-dependent adhesion to fibronectin is essential for cancer cell migration
Mukai, M.; Togawa, A.; Imamura, F.; Iwasaki, T.; Ayaki, M.; Mammoto, T.; Nakamura, H.; Tatsuta, M.; Inoue, M.
Anticancer Research 22(6a): 3175-3184
2002
ISSN/ISBN: 0250-7005 PMID: 12530062 Document Number: 545939
Co-stimulation with lysophosphatidic acid (LPA) and fibronectin (FN) is essential for migration of rat ascites hepatoma MMI cells. We examined the roles of LPA and FN in Rho-FAK pathway to migration. We evaluated the morphology, phagokinetic motility and the status of Rho activation and tyrosine-phosphorylation of FAK after stimulation of MMI or HT-1080 cells with LPA + FN or each alone. On FN-coated dishes without LPA, MM1 cells could not migrate and harbored undetectable levels of activated RhoA. Stimulation with LPA + FN enabled the MM1 cells to migrate and bear active RhoA and sustained tyrosine-phosphorylation of FAK. To the contrary, HT-1080 cells could migrate and harbored a significant amount of active RhoA accompanied by sustained tyrosine-phosphorylation of FAK even without LPA. Rho-dependent adhesion to FN leading to sustained tyrosine-phosphorylation of FAK is essential for cancer cell migration.