Title :

ERRα promotes breast cancer cell dissemination to bone by increasing RANK expression in primary breast tumors

Author(s) :

Vargas, G [Auteur]
Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases [LYOS]
Bouchet, M [Auteur]
Institut de Génomique Fonctionnelle de Lyon [IGFL]
Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases [LYOS]
Bouazza, L [Auteur]
Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases [LYOS]
Reboul, P [Auteur]
Ingénierie Moléculaire et Physiopathologie Articulaire [IMoPA]
Boyault, C [Auteur]
Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) [IAB]
Gervais, M [Auteur]
Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases [LYOS]
Kan, C [Auteur]
The University of Sydney
Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases [LYOS]
Benetollo, C [Auteur]
Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center [CRNL]
Brevet, M [Auteur]
Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases [LYOS]
Croset, M [Auteur]
Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases [LYOS]
Mazel, M [Auteur]
Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 [AIDMP]
Cayrefourcq, L [Auteur]
Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 [AIDMP]
Geraci, S [Auteur]
Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases [LYOS]
Vacher, S [Auteur]
Institut Curie [Paris]
Pantano, F [Auteur]
Università Campus Bio-Medico di Roma / University Campus Bio-Medico of Rome [ UCBM]
Filipits, M [Auteur]
Medizinische Universität Wien = Medical University of Vienna
Driouch, K [Auteur]
Institut Curie [Paris]
Bieche, I [Auteur]
Institut Curie [Paris]
Gnant, M. [Auteur]
Medizinische Universität Wien = Medical University of Vienna
Jacot, W [Auteur]
Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM]
Aubin, J.E. [Auteur]
Duterque-Coquillaud, M [Auteur]
Mécanismes de tumorigenèse et thérapies ciblées
Institut de biologie de Lille - IBL [IBLI]
Alix-Panabières, C [Auteur]
Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 [AIDMP]
Clézardin, P [Auteur]
Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases [LYOS]
Bonnelye, E [Auteur]
Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases [LYOS]

Publisher :

Nature Publishing Group

Publication date :

2019-02

HAL domain(s) :

Sciences du Vivant [q-bio]/Cancer
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Génomique, Transcriptomique et Protéomique [q-bio.GN]

English abstract : [en]

Bone is the most common metastatic site for breast cancer. Estrogen-related-receptor alpha (ERRα) has been implicated in cancer cell invasiveness. Here, we established that ERRα promotes spontaneous metastatic dissemination ...
Show more >Bone is the most common metastatic site for breast cancer. Estrogen-related-receptor alpha (ERRα) has been implicated in cancer cell invasiveness. Here, we established that ERRα promotes spontaneous metastatic dissemination of breast cancer cells from primary mammary tumors to the skeleton. We carried out cohort studies, pharmacological inhibition, gain-of-function analyses in vivo and cellular and molecular studies in vitro to identify new biomarkers in breast cancer metastases. Meta-analysis of human primary breast tumors revealed that high ERRα expression levels were associated with bone but not lung metastases. ERRα expression was also detected in circulating tumor cells from metastatic breast cancer patients. ERRα overexpression in murine 4T1 breast cancer cells promoted spontaneous bone micro-metastases formation when tumor cells were inoculated orthotopically, whereas lung metastases occurred irrespective of ERRα expression level. In vivo, Rank was identified as a target for ERRα. That was confirmed in vitro in Rankl stimulated tumor cell invasion, in mTOR/pS6K phosphorylation, by transactivation assay, ChIP and bioinformatics analyses. Moreover, pharmacological inhibition of ERRα reduced primary tumor growth, bone micro-metastases formation and Rank expression in vitro and in vivo. Transcriptomic studies and meta-analysis confirmed a positive association between metastases and ERRα/RANK in breast cancer patients and also revealed a positive correlation between ERRα and BRCA1 mut carriers. Taken together, our results reveal a novel ERRα/RANK axis by which ERRα in primary breast cancer promotes early dissemination of cancer cells to bone. These findings suggest that ERRα may be a useful therapeutic target to prevent bone metastases.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL

Submission date :

2021-08-25T01:30:35Z