Objectif Ligands of the Transfroming Growth Factor-beta (TGF-beta) superfamily control numerous cellular processes such as proliferation, apoptosis, differentiation, adhesion and mobility. As a result, it is well established that they play an essential role in cancer. TGF-beta signalling has been implicated in both tumour suppression and progression. TGF-beta signals predominantly through receptor-regulated Smads (R-Smads), Smad2 and Smad3, but several lines of evidence from the Hill’s lab suggest that TGF-beta can also strongly induce phosphorylation and consequently signalling by Smad1 and Smad5 in epithelial cells. Moreover, our recent results have shown that Smad1/5 activation by TGF-beta is not required for its growth inhibitory effects, but rather is specifically required for TGF-beta-induced anchorage-independent growth, suggesting a relevant role of this novel mode of signalling in tumor progression. The first aim of this project is the accurate molecular description of TGF-beta-induced activation of Smad1/5. We will focus both on the receptor complexes responsible and the types of Smad complexes that result. Then, we will study which genes are induced by this novel mode of TGF-beta signalling. Finally, its functional relevance in normal epithelial cells and in tumorigenesis will be assessed. If we can show that this novel branch of TGF-beta signalling plays a role in tumour growth, then it could provide a good therapeutic target in cancer. Champ scientifique sciences médicales et de la santémédecine cliniqueoncologie Mots‑clés Cancer Molecular biology Smad1/5 TGF-beta Tumor progression systems biology Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-IEF-2008 - Marie Curie Action: "Intra-European Fellowships for Career Development" Appel à propositions FP7-PEOPLE-IEF-2008 Voir d’autres projets de cet appel Régime de financement MC-IEF - Intra-European Fellowships (IEF) Coordinateur CANCER RESEARCH UK LBG Adresse 2 redman place E20 1JQ London Royaume-Uni Voir sur la carte Région London Inner London — West Camden and City of London Type d’activité Research Organisations Contact administratif Louisa Jacobs (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Contribution de l’UE Aucune donnée
