STAT3 is an oncoprotein overexpressed in different types of tumors, including prostate cancer (PCa), and its activity is modulated by a variety of post-translational modifications (PTMs). Prostate cancer represents the most common cancer diagnosed in men, and each phase of tumor progression displays specific cellular conditions: inflammation is predominant in tumor's early stage, whereas oxidative stress is typical of clinically advanced PCa. The aim of this research is to assess the correspondence between the stimulus-specificity of STAT3 PTMs and definite STAT3-mediated transcriptional programs, in order to identify new suitable pharmacological targets for PCa treatment. Experiments were performed on less-aggressive LNCaP and more aggressive DU-145 cell lines, simulating inflammatory and oxidative-stress conditions. Cellular studies confirmed pY705-STAT3 as common denominator of all STAT3-mediated signaling. In addition, acK685-STAT3 was found in response to IL-6, whereas glutC328/542-STAT3 and pS727-STAT3 occurred upon tert-butyl hydroperoxyde (tBHP) treatment. Obtained results also provided evidence of an interplay between STAT3 PTMs and specific protein interactors such as P300 and APE1/Ref-1. In accordance with these outcomes, mRNA levels of STAT3-target genes seemed to follow the differing STAT3 PTMs. These results highlighted the role of STAT3 and its PTMs as drivers in the progression of PCa.
International journal of molecular sciences. 2019 Apr 12*** epublish ***
Rossana Cocchiola, Elisabetta Rubini, Fabio Altieri, Silvia Chichiarelli, Giuliano Paglia, Donatella Romaniello, Stefania Carissimi, Alessandra Giorgi, Flavia Giamogante, Alberto Macone, Giacomo Perugia, Aymone Gurtner, Margherita Eufemi
Department of Biochemical Sciences "A. Rossi Fanelli" and Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, P.le A. Moro 5, 00185 Rome, Italy. ., Department of Biochemical Sciences "A. Rossi Fanelli" and Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, P.le A. Moro 5, 00185 Rome, Italy. ., Department of Biochemical Sciences "A. Rossi Fanelli" and Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, P.le A. Moro 5, 00185 Rome, Italy. ., Department of Biochemical Sciences "A. Rossi Fanelli" and Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, P.le A. Moro 5, 00185 Rome, Italy. ., Department of Biochemical Sciences "A. Rossi Fanelli" and Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, P.le A. Moro 5, 00185 Rome, Italy. ., Department of Biological Regulation, Weizmann Institute of Science, 234 Herzl Street, 7610001 Rehovot, Israel. ., Department of Biochemical Sciences "A. Rossi Fanelli" and Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, P.le A. Moro 5, 00185 Rome, Italy. ., Department of Biochemical Sciences "A. Rossi Fanelli" and Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, P.le A. Moro 5, 00185 Rome, Italy. ., Department of Biochemical Sciences "A. Rossi Fanelli" and Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, P.le A. Moro 5, 00185 Rome, Italy. ., Department of Biochemical Sciences "A. Rossi Fanelli" and Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, P.le A. Moro 5, 00185 Rome, Italy. ., Department of Gynecological-Obstretic Science and Urologic Sciences, Sapienza University, V.le Dell'Università, 00185 Rome, Italy. ., Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute; via Elio Chianesi, 53, 00144 Rome, Italy. ., Department of Biochemical Sciences "A. Rossi Fanelli" and Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, P.le A. Moro 5, 00185 Rome, Italy. .