%0 Journal Article
%A Sáez-Martínez, Prudencio
%A Jiménez-Vacas, Juan M.
%A León-González, Antonio J.
%A Herrero-Aguayo, Vicente
%A Montero Hidalgo, Antonio J.
%A Gómez-Gómez, Enrique
%A Sánchez-Sánchez, Rafael
%A Requena-Tapia, María J.
%A Castaño, Justo P.
%A Gahete, Manuel D.
%A Luque, Raúl M.
%T Unleashing the Diagnostic, Prognostic and Therapeutic Potential of the Neuronostatin/GPR107 System in Prostate Cancer
%D 2020
%U http://hdl.handle.net/10668/3883
%X Certain 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.
%K Prostate cancer
%K Castration resistant prostate cancer
%K Neuronostatin
%K G protein-coupled receptor GPR107
%K Diagnostic/prognostic biomarker
%K Therapeutic target
%K Somatostatin-system
%K Splicing
%K Neoplasias de la próstata
%K Neoplasias de la próstata resistentes a la castración
%K Somatostatina
%K Andalucía
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