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

Anticancer Res. Nov-Dec 2002;22(6A):3175-84.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion / physiology
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Fibronectins / metabolism
  • Fibronectins / pharmacology*
  • Fibronectins / physiology
  • Fibrosarcoma / pathology*
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Humans
  • Liver Neoplasms, Experimental / pathology*
  • Lysophospholipids / metabolism
  • Lysophospholipids / pharmacology*
  • Lysophospholipids / physiology
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism*
  • Rats
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Tumor Cells, Cultured
  • Tyrosine / metabolism
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • Fibronectins
  • Lysophospholipids
  • Tyrosine
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • PTK2 protein, human
  • Ptk2 protein, rat
  • rhoA GTP-Binding Protein