Objectif Breast cancer is diagnosed in ~1.4 million women worldwide and ~500,000 lives are lost to the disease annually. Patients may do well after surgery and initial treatment, but drug resistant and fatal metastases often develop. Improved treatment options are urgently needed. The connecting thread of this project is the identification of epigenetic drivers of breast cell fate, tumor heterogeneity and metastasis.Tumor heterogeneity impinges on prognosis, response to therapy, and metastasis and is one of the most important and clinically relevant areas of cancer research. Tumor heterogeneity results from genetic and epigenetic alterations that enhance the plasticity and fitness of cancer cells in the face of hurdles like the metastatic cascade and anti-cancer therapies. Unfortunately, the driving molecular mechanisms remain unclear, particularly the potential interplay between signalling pathways and epigenetic programs.This interdisciplinary project uses pathophysiologically relevant models and state-of-the-art technologies to identify molecular mechanisms underlying crosstalk between key signalling pathways and epigenetic programs in the normal and neoplastic breast. We hypothesize that interfering with these programs will decrease tumor heterogeneity.We will address the effects of:- SHP2/ERK signalling on the epigenetic programs of tumor-initiating cells (Aim 1)- PI3K pathway hyperactivation on the epigenetic programs underpinning cell plasticity (Aim 2)- Epigenetic regulators on normal mammary cell self-renewal and on metastasis (Aim 3)By investigating the integrated effects of key signalling pathways and epigenetic programs in normal and neoplastic breast, this multipronged project will identify and validate mechanisms of cell plasticity. The derived mechanistic understanding will generate means to interfere with tumor heterogeneity and thus improve the efficacy of anti-cancer therapies and ultimately the clinical outcome for patients with breast cancer. Champ scientifique medical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologybreast cancermedical and health sciencesclinical medicineoncologyskin cancerbasal cellsmedical and health sciencesclinical medicinetransplantationnatural sciencesbiological sciencesgeneticsepigenetics Mots‑clés Phosphatases- PI3K- signaling- Epigenetics- stem cells Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-ADG-2015 - ERC Advanced Grant Appel à propositions ERC-2015-AdG Voir d’autres projets de cet appel Régime de financement ERC-ADG - Advanced Grant Institution d’accueil UNIVERSITAT BASEL Contribution nette de l'UE € 519 375,00 Adresse PETERSPLATZ 1 4051 Basel Suisse Voir sur la carte Région Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 2 499 250,00 Bénéficiaires (3) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire UNIVERSITAT BASEL Suisse Contribution nette de l'UE € 519 375,00 Adresse PETERSPLATZ 1 4051 Basel Voir sur la carte Région Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 2 499 250,00 Tiers Entité juridique autre qu’un sous-traitant qui est affiliée ou juridiquement liée à un participant. L’entité réalise des travaux dans les conditions prévues par la convention de subvention, fournit des biens ou des services pour l’action, mais n’a pas signé la convention de subvention. Le tiers respecte les règles applicables au participant qui lui est lié dans le cadre de la convention de subvention en ce qui concerne l’éligibilité des coûts et le contrôle des dépenses. UNIVERSITATSSPITAL BASEL Suisse Contribution nette de l'UE € 1 979 875,00 Adresse HEBELSTRASSE 32 4031 Basel Voir sur la carte Région Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt Type d’activité Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments) Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 979 875,00 FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION Participation terminée Suisse Contribution nette de l'UE € 0,00 Adresse MAULBEERSTRASSE 66 4058 Basel Voir sur la carte Région Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total Aucune donnée