Epithelial-mesenchymal transition in prostate cancer: an overview

// Micaela Montanari 1,2 , Sabrina Rossetti 1 , Carla Cavaliere 1,3 , Carmine D’Aniello 1,4 , Maria Gabriella Malzone 1,5 , Daniela Vanacore 1 , Rossella Di Franco 1,6 , Elvira La Mantia 1,5 , Gelsomina Iovane 1,7 , Raffaele Piscitelli 1 , Raffaele Muscariello 8 , Massimiliano Berretta 9 , Sisto Perdonà 8 , Paolo Muto 6 , Gerardo Botti 5,10 , Attilio Antonio Montano Bianchi 11 , Bianca Maria Veneziani 2 and Gaetano Facchini 1,7 1 Progetto ONCONET2.0, Linea Progettuale 14 per L’implementazione della Prevenzione e Diagnosi Precoce del Tumore alla Prostata e Testicolo, Regione Campania, Italy 2 Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, Naples, Italy 3 Department of Onco-Ematology Medical Oncology, S.G. Moscati Hospital of Taranto, Taranto, Italy 4 Division of Medical Oncology, A.O.R.N. dei COLLI “Ospedali Monaldi-Cotugno-CTO”, Naples, Italy 5 Pathology Unit, Istituto Nazionale Tumori “Fondazione G. Pascale”, IRCCS, Naples, Italy 6 Radiation Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘Fondazione Giovanni Pascale’, IRCCS, Naples, Italy 7 Department of Uro-Gynaecological Oncology, Division of Medical Oncology, Istituto Nazionale Tumori ‘Fondazione G. Pascale’, IRCCS, Naples, Italy 8 Department of Uro-Gynaecological Oncology, Division of Urology, Istituto Nazionale Tumori ‘Fondazione G. Pascale’, IRCCS, Naples, Italy 9 Department of Medical Oncology, CRO Aviano, National Cancer Institute, Aviano, Italy 10 Scientific Directorate, Istituto Nazionale Tumori ‘Fondazione G. Pascale’, IRCCS, Naples, Italy 11 Directorate-General for Management, Istituto Nazionale Tumori ‘Fondazione G. Pascale’, IRCCS, Naples, Italy Correspondence to: Micaela Montanari, email: // Keywords : prostate cancer; epithelial-mesenchymal transition; androgen receptor; TGF-β signaling; EGF/EGFR Received : November 10, 2016 Accepted : February 15, 2017 Published : February 25, 2017 Abstract Prostate cancer is a main urological disease associated with significant morbidity and mortality. Radical prostatectomy and radiotherapy are potentially curative for localized prostate cancer, while androgen deprivation therapy is the initial systemic therapy for metastatic prostate disease. However, despite temporary response, most patients relapse and evolve into castration resistant cancer. Epithelial-mesenchymal transition (EMT) is a complex gradual process that occurs during embryonic development and/or tumor progression. During this process, cells lose their epithelial characteristics and acquire mesenchymal features. Increasing evidences indicate that EMT promotes prostate cancer metastatic progression and it is closely correlated with increased stemness and drug resistance. In this review, we discuss the main molecular events that directly or indirectly govern the EMT program in prostate cancer, in order to better define the role and the mechanisms underlying this process in prostate cancer progression and therapeutic resistance.