Sustained tyrosine-phosphorylation of FAK through Rho-dependent adhesion to fibronectin is essential for cancer cell migration. Anticancer Res 2002;22(6A):3175-84
Date
01/18/2003Pubmed ID
12530062Scopus ID
2-s2.0-0036870596 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
BACKGROUND: 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.
MATERIALS AND METHODS: 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.
RESULTS: 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.
CONCLUSION: Rho-dependent adhesion to FN leading to sustained tyrosine-phosphorylation of FAK is essential for cancer cell migration.
Author List
Mukai M, Togawa A, Imamura F, Iwasaki T, Ayaki M, Mammoto T, Nakamura H, Tatsuta M, Inoue MAuthor
Tadanori Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Adhesion
Cell Movement
Fibronectins
Fibrosarcoma
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
Humans
Liver Neoplasms, Experimental
Lysophospholipids
Phosphorylation
Protein-Tyrosine Kinases
Rats
Signal Transduction
Tumor Cells, Cultured
Tyrosine
rhoA GTP-Binding Protein