Tumor Suppressor PTEN Inhibition of Cell Invasion, Migration, and Growth: Differential Involvement of Focal Adhesion Kinase and p130Cas

摘要: PTEN/MMAC1 is a major new tumor suppressor gene that encodes dual-specificity phosphatase with sequence similarity to the cytoskeletal protein tensin. Recently, we reported PTEN dephosphorylates focal adhesion kinase (FAK) and inhibits cell migration, spreading, formation. Here, effects of on invasion, growth as well involvement FAK p130 Crk-associated substrate (p130Cas) were investigated in U87MG glioblastoma cells missing PTEN. Cell down-regulated by expression phosphatase-active forms but not an inactive domain; these correlated decreased tyrosine phosphorylation levels p130Cas. Overexpression concomitant resulted increased total p130Cas effectively antagonized invasion migration partially growth. without affecting those FAK; however, although could reverse inhibition it did rescue cells. In contrast FAK, be shown interact cells, was dephosphorylated directly vitro. These results suggest important roles phenotype progression, are mediated distinct downstream pathways diverge at level FAK.