Unleashing the Diagnostic, Prognostic and Therapeutic Potential of the Neuronostatin/GPR107 System in Prostate Cancer
| Autor: | Rafael Sánchez-Sánchez, Raúl M. Luque, Manuel D. Gahete, Enrique Gómez-Gómez, Vicente Herrero-Aguayo, Justo P. Castaño, Prudencio Sáez-Martínez, Antonio J. Montero Hidalgo, Antonio J. León-González, Juan M. Jiménez-Vacas, M.J. Requena-Tapia |
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| Přispěvatelé: | [Sáez-Martínez,P, Jiménez-Vacas,JM, León-González,AJ, Herrero-Aguayo,V, Montero Hidalgo,AJ, Gómez-Gómez,E, Sánchez-Sánchez,R, Requena-Tapia,MJ, Castaño,JP, Gahete,MD, Luque,RM] Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Cordoba, Spain. [Sáez-Martínez,P, Luque,RM] Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Cordoba, Spain. [Sáez-Martínez,P, Luque,RM] Hospital Universitario Reina Sofía (HURS), Cordoba, Spain. [Sáez-Martínez,P, Luque,RM] Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, (CIBERobn), Cordoba, Spain. [Gómez-Gómez,E, Requena-Tapia,MJ] Urology Service, HURS/IMIBIC, Cordoba, Spain. [Sánchez-Sánchez,R] Anatomical Pathology Service, HURS, Cordoba, Spain., This research was funded by Instituto de Salud Carlos III, co-funded by European Union (ERDF/ESF, 'Investing in your future') [PI16/00264, PI17/02287, CD16/00092], MINECO/MECD (FPU17/00263, FPU16/06190, FPU18/02485, BFU2016-80360-R), Junta de Andalucia (BIO-0139), and CIBERobn. CIBER is an initiative of Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain. |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Diagnostic/prognostic biomarker Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings] castration resistant prostate cancer Neoplasias de la próstata Anatomy::Urogenital System::Genitalia::Genitalia Male::Prostate [Medical Subject Headings] Cell neuronostatin Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Membrane Proteins::Receptors Cell Surface::Receptors G-Protein-Coupled [Medical Subject Headings] lcsh:Medicine MMP9 Splicing Diseases::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms Male::Prostatic Neoplasms::Prostatic Neoplasms Castration-Resistant [Medical Subject Headings] urologic and male genital diseases Metastasis Somatostatin-system Prostate cancer 0302 clinical medicine Information Science::Information Science::Computing Methodologies::Artificial Intelligence [Medical Subject Headings] Medicine diagnostic/prognostic biomarker CDKN2D Receptor EZH2 therapeutic target General Medicine Chemicals and Drugs::Biological Factors::Antigens::Antigens Nuclear::Ki-67 Antigen [Medical Subject Headings] prostate cancer medicine.anatomical_structure 030220 oncology & carcinogenesis Castration resistant prostate cancer G protein‐coupled receptor GPR107 Somatostatin‐system G protein-coupled receptor GPR107 Therapeutic target somatostatin-system Neuronostatin Check Tags::Male [Medical Subject Headings] Article 03 medical and health sciences splicing LNCaP Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Hormones Hormone Substitutes and Hormone Antagonists::Hormones::Androgens [Medical Subject Headings] Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell Proliferation [Medical Subject Headings] Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings] Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Down-Regulation [Medical Subject Headings] business.industry Analytical Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures Operative::Urogenital Surgical Procedures::Castration [Medical Subject Headings] Neoplasias de la próstata resistentes a la castración Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Membrane Proteins::Receptors Cell Surface::Receptors G-Protein-Coupled::Receptors Somatostatin [Medical Subject Headings] lcsh:R Andalucía medicine.disease Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Endopeptidases::Metalloendopeptidases::Collagenases::Matrix Metalloproteinase 9 [Medical Subject Headings] Somatostatina 030104 developmental biology Chemicals and Drugs::Hormones Hormone Substitutes and Hormone Antagonists::Hormones::Peptide Hormones::Ghrelin [Medical Subject Headings] Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Neoplasm Proteins::Oncogene Proteins::Proto-Oncogene Proteins::Proto-Oncogene Proteins c-akt [Medical Subject Headings] Cancer research Analytical Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings] business |
| Zdroj: | Journal of Clinical Medicine, Vol 9, Iss 1703, p 1703 (2020) Journal of Clinical Medicine Volume 9 Issue 6 Journal of Clinical Medicine 9(6), 1703 (2020) Helvia. Repositorio Institucional de la Universidad de Córdoba instname Helvia: Repositorio Institucional de la Universidad de Córdoba Universidad de Córdoba |
| ISSN: | 2077-0383 |
| Popis: | 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&prime 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. |
| Databáze: | OpenAIRE |
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