Linking TGF-beta-mediated Cdc25A Inhibition and Cytoskeletal Tegulation through RhoA/p160ROCK Signaling

Abstract

Transforming growth factor-beta (TGF-b) can mediate G1/S cell-cycle inhibition and changes in the cytoskeletal organization through multiple parallel downstream signaling pathways. Recent findings regarding TGF-b-mediated cell-cycle checkpoint control and epithelial to mesenchymal transition have converged to the RhoA/p160ROCK signaling pathway. The activation of TGF-b-mediated p160ROCK rapidly inhibits the Cdc25A phosphatase as a component of the G1/S checkpoint control at the time cytoskeletal re-organization occurs. This can be likened to the ability to preserve genomic integrity in circumstances of genotoxic stress. The inactivation of the RhoA/p160ROCK pathway may be a mechanism by which cancer cells bypass growth inhibition even in the presence of TGF-b.