Sustained tyrosine-phosphorylation of FAK through Rho-dependent adhesion to fibronectin is essential for cancer cell migration.
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.


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.


CONCLUSIONS
Rho-dependent adhesion to FN leading to sustained tyrosine-phosphorylation of FAK is essential for cancer cell migration.
Mukai
Mutsuko
M
Department of Tumor Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan. mukai-mu@mc.pref.osaka.jp
Togawa
Atsushi
A
Imamura
Fumio
F
Iwasaki
Teruo
T
Ayaki
Masako
M
Mammoto
Tadanori
T
Nakamura
Hiroyuki
H
Tatsuta
Masaharu
M
Inoue
Masahiro
M
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D005354:Fibrosarcoma / Q000473:pathology*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D005353:Fibronectins; D008246:Lysophospholipids; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496052:Ptk2 protein, rat; D020742:rhoA GTP-Binding Protein