Activation of the Tumor Suppressor PP2A Emerges as a Potential Therapeutic Strategy for Treating Prostate Cancer.
Activation of the Tumor Suppressor PP2A Emerges as a Potential Therapeutic Strategy for Treating Prostate Cancer.
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DOI：
10.3390/md13063276
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发表时间：
2015-05-27
期刊：
影响因子：
5.4
通讯作者：
García-Foncillas J
中科院分区：
文献类型：
--
作者：
Cristóbal I;González-Alonso P;Daoud L;Solano E;Torrejón B;Manso R;Madoz-Gúrpide J;Rojo F;García-Foncillas J
Protein phosphatase 2A (PP2A) is a tumor suppressor complex that has recently been reported as a novel and highly relevant molecular target in prostate cancer (PCa). However, its potential therapeutic value remains to be fully clarified. We treated PC-3 and LNCaP cell lines with the PP2A activators forskolin and FTY720 alone or combined with the PP2A inhibitor okadaic acid. We examined PP2A activity, cell growth, prostasphere formation, levels of PP2A phosphorylation, CIP2A and SET expression, and AKT and ERK activation. Interestingly, both forskolin and FTY720 dephosphorylated and activated PP2A, impairing proliferation and prostasphere formation and inducing changes in AKT and ERK phosphorylation. Moreover, FTY720 led to reduced CIP2A levels. Treatment with okadaic acid impaired PP2A activation thus demonstrating the antitumoral PP2A-dependent mechanism of action of both forskolin and FTY720. Levels of PP2A phosphorylation together with SET and CIP2A protein expression were studied in 24 PCa patients and both were associated with high Gleason scores and presence of metastatic disease. Altogether, our results suggest that PP2A inhibition could be involved in PCa progression, and the use of PP2A-activating drugs might represent a novel alternative therapeutic strategy for treating PCa patients.
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影响因子：
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作者：
Rincón R;Cristóbal I;Zazo S;Arpí O;Menéndez S;Manso R;Lluch A;Eroles P;Rovira A;Albanell J;García-Foncillas J;Madoz-Gúrpide J;Rojo F
通讯作者：
Rojo F
影响因子：
8.8
作者：
Corcoran, N. M.;Hovens, C. M.;Michael, M.;Rosenthal, M. A.;Costello, A. J.
通讯作者：
Costello, A. J.
DOI：
10.1016/s1470-2045(12)70558-2
发表时间：
2013-05
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Perrotti D;Neviani P
通讯作者：
Neviani P
DOI：
10.1158/1541-7786.mcr-13-0542
发表时间：
2014-06
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Farrell AS;Allen-Petersen B;Daniel CJ;Wang X;Wang Z;Rodriguez S;Impey S;Oddo J;Vitek MP;Lopez C;Christensen DJ;Sheppard B;Sears RC
通讯作者：
Sears RC
DOI：
10.1186/1756-9966-29-136
发表时间：
2010-10-21
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Vaarala MH;Väisänen MR;Ristimäki A
通讯作者：
Ristimäki A