Obiettivo Cell survival depends on the integration of numerous signals provided by the extracellular environment. Activation of signal transduction by transmembrane receptors is assumed to occur following interaction with a specific ligand. However, some receptors, called dependence receptors (DRs) have been shown to mediate a signal in the absence of ligand. These receptors share the ability to mediate two opposing signals: in the presence of their cognate ligand, they transduce survival signals, whereas, in the absence of their ligand, they induce apoptosis. This idea was initially proposed for the Deleted in Colorectal Cancer (DCC) receptor, and now, number of such receptors has increased over the past ten years. There are now a dozen DRs described including the netrin-1 receptors DCC and UNC5H1-4, RET, TrkC, neogenin, and Patched. Identifying new dependence receptors is an important challenge since it causes a paradigm shift of a specific signalling pathway and alters our understanding of the developmental and physiological processes involving such receptors. For example, the DRs concept revealed a novel role for DCC in colon cancer, for netrin-1 in breast cancer metastasis and angiogenesis. Despite sharing little structural homology, all DRs contain a Dependence Associated Receptor Transmembrane (DART) motif, induce apoptosis in the absence of ligand and are cleaved by caspases to release a pro-apoptotic fragment. Preliminary data shows that Notch3 shares these characteristics. Notch3 is a member of the family of Notch receptors which regulates various stages in development and cancer as the receptors control cellular differentiation, proliferation and death. Notch3 has never been studied as a dependence receptor and the aim of this application is thus to further characterise Notch3 dependence signalling. We will study the mechanisms of Notch3-induced cell death and its relevance in physiological models, the involution of the mammary gland and lung cancers. Campo scientifico medical and health sciencesclinical medicineoncologylung cancermedical and health sciencesclinical medicineoncologybreast cancermedical and health sciencesclinical medicineoncologycolorectal cancer Programma(i) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) FP7-PEOPLE-2009-IEF - Marie Curie Action: "Intra-European Fellowships for Career Development" Invito a presentare proposte FP7-PEOPLE-2009-IEF Vedi altri progetti per questo bando Meccanismo di finanziamento MC-IEF - Intra-European Fellowships (IEF) Coordinatore CENTRE DE LUTTE CONTRE LE CANCER LEON BERARD Contributo UE € 166 145,60 Indirizzo RUE LAENNEC 28 69373 Lyon Francia Mostra sulla mappa Regione Auvergne-Rhône-Alpes Rhône-Alpes Rhône Tipo di attività Research Organisations Contatto amministrativo Marina Rousseau-Tsangaris (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato
