Inhibitory role of RhoA on senescence-like growth arrest by a mechanism involving modulation of phosphatase activity.
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.
Park
Chaehwa
C
Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Kangnam-gu, Seoul 135-710, Republic of Korea. cpark@smc.samsung.co.kr
Lee
Inkyoung
I
Jang
Jun Ho
JH
Kang
Won Ki
WK
D000970:Antineoplastic Agents / Q000494:pharmacology; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000502:physiology*; D004317:Doxorubicin / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D000970:Antineoplastic Agents; D004317:Doxorubicin; D048052:Mitogen-Activated Protein Kinase 3; D010744:Phosphoric Monoester Hydrolases; D020742:rhoA GTP-Binding Protein