INHIBITION OF CELL-MIGRATION, SPREADING, AND FOCAL ADHESIONS BY TUMOR-SUPPRESSOR PTEN

The tumor suppressor PTEN is a phosphatase with sequence similarity to the cytoskeletal protein tensin. Here the cellular roles of PTEN were investigated. Overexpression of PTEN inhibited cell migration, wherea s antisense PTEN enhanced migration. Integrin-mediated cell spreading and the formation of focal adhesions were down-regulated by wild-type PTEN but not by PTEN with an inactive phosphatase domain. PTEN interac ted with the focal adhesion kinase FAK and reduced its tyrosine phosph orylation. Overexpression of FAK partially antagonized the effects of PTEN. Thus, PTEN phosphatase may function as a tumor suppressor by neg atively regulating cell interactions with the extracellular matrix.