RT Journal Article
T1 Unleashing the Diagnostic, Prognostic and Therapeutic Potential of the Neuronostatin/GPR107 System in Prostate Cancer
A1 Sáez-Martínez, Prudencio
A1 Jiménez-Vacas, Juan M.
A1 León-González, Antonio J.
A1 Herrero-Aguayo, Vicente
A1 Montero Hidalgo, Antonio J.
A1 Gómez-Gómez, Enrique
A1 Sánchez-Sánchez, Rafael
A1 Requena-Tapia, María J.
A1 Castaño, Justo P.
A1 Gahete, Manuel D.
A1 Luque, Raúl M.
K1 Prostate cancer
K1 Castration resistant prostate cancer
K1 Neuronostatin
K1 G protein-coupled receptor GPR107
K1 Diagnostic/prognostic biomarker
K1 Therapeutic target
K1 Somatostatin-system
K1 Splicing
K1 Neoplasias de la próstata
K1 Neoplasias de la próstata resistentes a la castración
K1 Somatostatina
K1 Andalucía
AB 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.
PB MDPI
YR 2020
FD 2020-06-02
LK http://hdl.handle.net/10668/3883
UL http://hdl.handle.net/10668/3883
LA en
NO Sáez-Martínez P, Jiménez-Vacas JM, León-González AJ, Herrero-Aguayo V, Montero Hidalgo AJ, Gómez-Gómez E, et al. Unleashing the Diagnostic, Prognostic and Therapeutic Potential of the Neuronostatin/GPR107 System in Prostate Cancer. J Clin Med. 2020 Jun 2;9(6):1703
DS RISalud
RD Apr 7, 2025