Sáez-Martínez, PrudencioJiménez-Vacas, Juan MLeón-González, Antonio JHerrero-Aguayo, VicenteMontero Hidalgo, Antonio JGómez-Gómez, EnriqueSánchez-Sánchez, RafaelRequena-Tapia, María JCastaño, Justo PGahete, Manuel DLuque, Raúl M2025-01-072025-01-072020-06-022077-0383https://hdl.handle.net/10668/25811Certain components of the somatostatin-system play relevant roles in Prostate Cancer (PCa), whose most aggressive phenotype (Castration-Resistant-PCa (CRPC)) remains lethal nowadays. However, neuronostatin and the G protein-coupled receptor 107 (GPR107), two novel members of the somatostatin-system, have not been explored yet in PCa. Consequently, we investigated the pathophysiological role of NST/GPR107-system in PCa. GPR107 expression was analyzed in well-characterized PCa patient's cohorts, and functional/mechanistic assays were performed in response to GPR107-silencing and NST-treatment in PCa cells (androgen-dependent (AD: LNCaP) and androgen-independent (AI: 22Rv1/PC-3), which are cell models of hormone-sensitive and CRPC, respectively), and normal prostate cells (RWPE-1 cell-line). GPR107 was overexpressed in PCa and associated with key clinical parameters (e.g., advance stage of PCa, presence of vascular invasion and metastasis). Furthermore, GPR107-silencing inhibited proliferation/migration rates in AI-PCa-cells and altered key genes and oncogenic signaling-pathways involved in PCa aggressiveness (i.e., KI67/CDKN2D/MMP9/PRPF40A, SST5TMD4/AR-v7/In1-ghrelin/EZH2 splicing-variants and AKT-signaling). Interestingly, NST treatment inhibited proliferation/migration only in AI-PCa cells and evoked an identical molecular response than GPR107-silencing. Finally, NST decreased GPR107 expression exclusively in AI-PCa-cells, suggesting that part of the specific antitumor effects of NST could be mediated through a GPR107-downregulation. Altogether, NST/GPR107-system could represent a valuable diagnostic and prognostic tool and a promising novel therapeutic target for PCa and CRPC.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/G protein-coupled receptor GPR107castration resistant prostate cancerdiagnostic/prognostic biomarkerneuronostatinprostate cancersomatostatin-systemsplicingtherapeutic targetresearch article32498336open access10.3390/jcm9061703PMC7355908https://www.mdpi.com/2077-0383/9/6/1703/pdfhttps://pmc.ncbi.nlm.nih.gov/articles/PMC7355908/pdf