Linking TGF-β-mediated Cdc25A inhibition and cytoskeletal regulation through RhoA/p160ROCK signaling

Abstract

Transforming growth factor-beta (TGF-β) can mediate G1/S cell-cycle inhibition and changes in the cytoskeletal organization through multiple parallel downstream signaling pathways. Recent findings regarding TGF-β-mediated cell-cycle checkpoint control and epithelial to mesenchymal transition have converged to the RhoA/p160ROCK signaling pathway. The activation of TGF-β-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-β.