FXYD5/Dysadherin is a new marker of prostate cancer progression and aggressiveness associated with epithelial-to-mesenchymal transition

RICARDO BELLO; MARÍA JOSÉ BESSO; MARÍA VICTORIA MENCUCCI; CRISTIAN MOIOLA; MARINA ROSSO; MÓNICA H. VAZQUEZ-LEVIN

Congreso; Andrology 2020: International Meeting of the ISA, EAA and DGA; 2020

Prostate Cancer (PCa) is the 2nd most frequent cancer diagnosed in men. Among mechanisms involved, Epithelial to Mesenchymal Transition (EMT) stands up, and Epithelial Cadherin (E-cadherin/CDH1) expression/function loss is an EMT hallmark. Decreased CDH1 was related to FXYD5/Dysadherin (FXYD5/Dys), a poor prognosis and metastasis marker in other tumors. Expression of EMT markers and FXYD5/Dys in PCa and their association with tumor aggressiveness were evaluated using bioinformatics, cell models and tumor samples. Gene-disease association analysis (DisGeNET) identified CDH1 among PCa 50 top-genes, and mutation analysis (COSMIC) showed 2.54% CDH1 mutations (57/2243). EMT markers and FYXD5/Dys expression analysis done in human PCa cell lines (metastatic potential null/low: LNCaP/C4-2/22Rv1; medium/high: C4-2B/DU-145/PC3) revealed lower CDH1 mRNA levels and higher ZEB1, SLUG, N-cadherin and Vimentin in PCa with medium/high metastatic potential (P