Linking TGF-beta-mediated Cdc25A inhibition and cytoskeletal regulation through RhoA/p160(ROCK) signaling.
Transforming growth factor-beta (TGF-beta) can mediate G(1)/S cell-cycle inhibition and changes in the cytoskeletal organization through multiple parallel downstream signaling pathways. Recent findings regarding TGF-beta-mediated cell-cycle checkpoint control and epithelial to mesenchymal transition have converged to the RhoA/p160(ROCK) signaling pathway. The activation of TGF-beta-mediated p160(ROCK)rapidly inhibits the Cdc25A phosphatase as a component of the G(1)/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/p160(ROCK) pathway may be a mechanism by which cancer cells bypass growth inhibition even in the presence of TGF-beta.
Brown
Kimberly
K
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Bhowmick
Neil A
NA
D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D003599:Cytoskeleton / Q000378:metabolism*; D018450:Disease Progression; D016193:G1 Phase; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016196:S Phase; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D020687:cdc25 Phosphatases / Q000378:metabolism*; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D016212:Transforming Growth Factor beta; D020687:cdc25 Phosphatases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; C517004:CDC25A protein, human; C517005:Cdc25a protein, mouse