Estrogen related receptor alpha in castration-resistant prostate cancer cells promotes tumor progression in bone
| Autor: | Claire Benetollo, Edith Bonnelye, Vincenzo Castronovo, Jennifer Rieusset, Thomas J. Rosol, Mathilde Bouchet, Anais Fradet, Akeila Bellahcene, Lamia Bouazza, Carine Delliaux, Philippe Clézardin, Martine Duterque-Coquillaud, Martine Croset, Casina Kan, Francesco Pantano, Xavier Leroy, Manon Gervais, Jane E. Aubin, Geoffrey Vargas, Yohann Bala |
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| Přispěvatelé: | Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanismes de la Tumorigénèse et Thérapies Ciblées (M3T) - UMR 8161 (M3T), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università Campus Bio-Medico di Roma / University Campus Bio-Medico of Rome ( UCBM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), College of Veterinary Medicine [Colombus], Ohio State University [Columbus] (OSU), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université de Liège, University of Toronto, This work was supported by the Association pour la recherche sur les tumeurs de la prostate (ARTP), the National Center for Scientific Research (CNRS) to EB and by the National Institute of Health and Medical Research (INSERM) and the University of Lyon1. AF was supported by the Ligue nationale contre le cancer and the Fondation pour la recherche médicale (FRM), MB, MG by the French National Cancer Institute (INCa), CD by the Institut Pasteur/Région Nord-Pas-de-Calais, GV by the Labex DEVweCAN and AB from the Belgian National Fund for Scientific Research. CK is a recipient of the H2020 Marie Sklodowska-Curie Individual Fellowship under agreement number (655777-miROMeS)., We are grateful to the Animalerie Lyon Est Conventionnelle (ALECS) and to D. Sahay for discussion., Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 (M3T), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
MESH: Signal Transduction MESH: Wnt-5a Protein/metabolism Male Vascular Endothelial Growth Factor A Pathology MESH: Cell Adhesion Molecules/metabolism [SDV]Life Sciences [q-bio] Cell [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology bone Prostate cancer Estrogen-related receptor alpha Mice 0302 clinical medicine MESH: Prostatic Neoplasms Castration-Resistant/genetics MESH: Tumor Microenvironment Tumor Microenvironment Medicine MESH: Animals MESH: Transforming Growth Factor beta1/metabolism MESH: Gene Expression Regulation Neoplastic prostate cancer 3. Good health Gene Expression Regulation Neoplastic Prostatic Neoplasms Castration-Resistant medicine.anatomical_structure Oncology Receptors Estrogen 030220 oncology & carcinogenesis MESH: Bone Neoplasms/metabolism Disease Progression MESH: Disease Progression MESH: Bone Neoplasms/genetics Research Paper Signal Transduction medicine.medical_specialty Stromal cell MESH: Cell Line Tumor medicine.drug_class MESH: Vascular Endothelial Growth Factor A/metabolism [SDV.CAN]Life Sciences [q-bio]/Cancer Bone Neoplasms Periostin Wnt-5a Protein Transforming Growth Factor beta1 03 medical and health sciences Stroma MESH: Prostatic Neoplasms Castration-Resistant/metabolism Cell Line Tumor Animals Humans MESH: Receptors Estrogen/metabolism [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Mice MESH: Humans MESH: Receptors Estrogen/genetics business.industry ERRα MESH: Bone Neoplasms/secondary medicine.disease microenvironment MESH: Male 030104 developmental biology Tumor progression Estrogen Cancer research business Cell Adhesion Molecules MESH: Neoplasm Transplantation Neoplasm Transplantation |
| Zdroj: | Oncotarget Oncotarget, Impact journals, 2016, 7 (47), pp.77071-77086. ⟨10.18632/oncotarget.12787⟩ Oncotarget, 2016, 7 (47), pp.77071-77086. ⟨10.18632/oncotarget.12787⟩ |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.12787⟩ |
| Popis: | International audience; Bone metastases are one of the main complications of prostate cancer and they are incurable. We investigated whether and how estrogen receptor-related receptor alpha (ERRalpha) is involved in bone tumor progression associated with advanced prostate cancer. By meta-analysis, we first found that ERRalpha expression is correlated with castration-resistant prostate cancer (CRPC), the hallmark of progressive disease. We then analyzed tumor cell progression and the associated signaling pathways in gain-of-function/loss-of-function CRPC models in vivo and in vitro. Increased levels of ERRalpha in tumor cells led to rapid tumor progression, with both bone destruction and formation, and direct impacts on osteoclasts and osteoblasts. VEGF-A, WNT5A and TGFbeta1 were upregulated by ERRalpha in tumor cells and all of these factors also significantly and positively correlated withERRalpha expression in CRPC patient specimens. Finally, high levels of ERRalpha in tumor cells stimulated the pro-metastatic factor periostin expression in the stroma, suggesting that ERRalpha regulates the tumor stromal cell microenvironment to enhance tumor progression. Taken together, our data demonstrate that ERRalpha is a regulator of CRPC cell progression in bone. Therefore, inhibiting ERRalpha may constitute a new therapeutic strategy for prostate cancer skeletal-related events. |
| Databáze: | OpenAIRE |
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