Inhibitory role of RhoA on senescence-like growth arrest by a mechanism involving modulation of phosphatase activity

Park C, Lee I, Jang JH, Kang WK
Source: FEBS Lett
Publication Date: (2007)
Issue: 581(20): 3800-4
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
Species: human
Tissue Origin: prostate
Nucleofector® I/II/2b
Recently, negative effects of phosphatase in tumorigenesis and metastasis have been suggested in various tumor types. In this study, we showed that RhoA activation modulated phosphatase during senescence-like arrest in human prostate cancer cells. Under senescence-inducing condition, decreased Erk phosphorylation was detected in caRhoA-transfected cells and inactivation of Erk, but not p38, prevented doxorubicin-induced cell senescence. Cells were induced to senescence by inhibition of phosphatase activity (VHR, MKP3, or PP2A) without additional cellular stress. Of interest, caRhoA prevented doxorubicin-induced decrease of phosphatase. Thus, we postulate that RhoA signaling may protect cells against cellular senescence by maintaining phosphatase activity and Erk dephosphorylation.