title: Activation of the Tumor Suppressor PP2A Emerges as a Potential Therapeutic Strategy for Treating Prostate Cancer.
abstract: 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.
authors.affiliation: Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz, UAM, University Hospital "Fundacion Jimenez Diaz", E-28040 Madrid, Spain. ion.cristobal@fjd.es.
authors.forename: Ion
authors.initials: I
authors.lastname: Cristóbal
authors.affiliation: Group of Cancer Biomarkers, Pathology Department, IIS-Fundacion Jimenez Diaz, UAM, E-28040 Madrid, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: González-Alonso
authors.affiliation: Group of Cancer Biomarkers, Pathology Department, IIS-Fundacion Jimenez Diaz, UAM, E-28040 Madrid, Spain. daoudlina@gmail.com.
authors.forename: Lina
authors.initials: L
authors.lastname: Daoud
authors.affiliation: Group of Cancer Biomarkers, Pathology Department, IIS-Fundacion Jimenez Diaz, UAM, E-28040 Madrid, Spain. esthersbasket4@gmail.com.
authors.forename: Esther
authors.initials: E
authors.lastname: Solano
authors.affiliation: Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz, UAM, University Hospital "Fundacion Jimenez Diaz", E-28040 Madrid, Spain. blanca.torrejonmoreno@gmail.com.
authors.forename: Blanca
authors.initials: B
authors.lastname: Torrejón
authors.affiliation: Group of Cancer Biomarkers, Pathology Department, IIS-Fundacion Jimenez Diaz, UAM, E-28040 Madrid, Spain. rebeca.manso@fjd.es.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Manso
authors.affiliation: Group of Cancer Biomarkers, Pathology Department, IIS-Fundacion Jimenez Diaz, UAM, E-28040 Madrid, Spain. jmadoz@fjd.es.
authors.forename: Juan
authors.initials: J
authors.lastname: Madoz-Gúrpide
authors.affiliation: Group of Cancer Biomarkers, Pathology Department, IIS-Fundacion Jimenez Diaz, UAM, E-28040 Madrid, Spain. frojo@fjd.es.
authors.forename: Federico
authors.initials: F
authors.lastname: Rojo
authors.affiliation: Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz, UAM, University Hospital "Fundacion Jimenez Diaz", E-28040 Madrid, Spain. blanca.torrejonmoreno@gmail.com.
authors.forename: Jesús
authors.initials: J
authors.lastname: García-Foncillas
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D054648:Protein Phosphatase 2 / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D005576:Colforsin; D019319:Okadaic Acid; D054648:Protein Phosphatase 2; D000068876:Fingolimod Hydrochloride
keywords: CIP2A; okadaic acid; p-PP2A; prostate cancer; therapy