Inhibition of Cell Migration, Spreading, and Focal Adhesions by Tumor Suppressor PTEN

TLDR

PTEN is a phosphatase related to the cytoskeletal protein tensin. The study investigated PTEN’s cellular roles. Overexpression of PTEN suppressed cell migration, spreading, and focal adhesion formation, reduced FAK phosphorylation, and these effects were partially reversed by FAK overexpression, indicating PTEN’s phosphatase activity negatively regulates cell–extracellular matrix interactions.

Abstract

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, whereas 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 interacted with the focal adhesion kinase FAK and reduced its tyrosine phosphorylation. Overexpression of FAK partially antagonized the effects of PTEN. Thus, PTEN phosphatase may function as a tumor suppressor by negatively regulating cell interactions with the extracellular matrix.