The PTEN lipid phosphatase domain is not required to inhibit invasion of glioma cells

The tumor suppressor PTEN negatively controls the phosphoinositide 3-kinase pathway for cell survival by dephosphorylating the phospholipid substrates phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisp hosphate. PTEN has been proposed to dephosphorylate focal adhesion kinase a nd is implicated in the regulation of cell spreading and motility, We analy zed the role of PTEN in invasion using the two highly infiltrative glioma c ell lines U87MG (which lacks functional PTEN) and LN229 (wild-type PTEN). A fter constitutive overexpression of wild-type and phosphatase-deficient (C1 24S) PTEN, we found significant inhibition of invasion (50-70%) independent of the PTEN status of the cell and of the catalytic core domain of PTEN, A lthough wild-type but not mutant (C124S) PTEN decreased PKB/Akt phosphoryla tion and induced a stellate morphology in U87MG cells, an accompanying redu ction of focal adhesion kinase phosphorylation was not seen. We conclude th at phosphatase-independent domains of PTEN markedly reduced the invasive po tential of glioma cells, defining a structural role for PTEN that regulates cell motility distinct of the PKB/Akt pathway.