Objective "While it is assumed that transmembrane receptors are active only in the presence of ligand, we have proposed that some receptors may also be active in the absence of ligand stimulation. These receptors, named “dependence receptors” (DRs) share the ability to transmit two opposite signals: in the presence of ligand, these receptors transduce various classical “positive” signals, whereas in the absence of ligand, they trigger apoptosis. The expression of dependence receptors thus creates cellular states of dependence for survival on their respective ligands. To date, more than fifteen such receptors have been identified, including the netrin-1 receptors DCC (Deleted in Colorectal Cancer) and UNC5H1-4, some integrins, RET, EPHA4, TrkA, TrkC and the Sonic Hedgehog receptor Patched (Ptc). Even though the interest in this notion is increasing, two main questions remain poorly understood: (i) how very different receptors, with only modest homology, are able to trigger apoptosis when unengaged by their respective ligand, and (ii) what are the respective biological roles of this pro-apoptotic activity in vivo. We have hypothesized that the DRs pro-apoptotic activity is a mechanism that determines and regulates the territories of migration/localization of cells during embryonic development. We also demonstrated that this may be a mechanism that limits tumor growth and metastasis. The goal of the present project is, based on the study of a relatively small number of these receptors –i.e. DCC, UNC5H, RET, TrkC, Ptc- with a specifically larger emphasis on netrin-1 receptors, to address (i) the common and divergent cell signaling mechanisms triggering apoptosis downstream of these receptors and (ii) the physiological and pathological roles of these DRs on development of neoplasia in vivo. This latter goal will allow us to investigate how this pro-apoptotic activity can be of use to improve and diversify alternative anti-cancer therapeutic approaches." Fields of science natural sciencesbiological sciencescell biologycell signalingnatural sciencesbiological sciencesdevelopmental biologymedical and health sciencesclinical medicineoncologycolorectal cancer Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Call for proposal ERC-2011-ADG_20110310 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Coordinator UNIVERSITE LYON 1 CLAUDE BERNARD Address Boulevard du 11 novembre 1918 num43 69622 Villeurbanne cedex France See on map Region Auvergne-Rhône-Alpes Rhône-Alpes Rhône Activity type Higher or Secondary Education Establishments Principal investigator Patrick Mehlen (Dr.) Administrative Contact Javier Olaiz (Dr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITE LYON 1 CLAUDE BERNARD France EU contribution € 2 485 037,00 Address Boulevard du 11 novembre 1918 num43 69622 Villeurbanne cedex See on map Region Auvergne-Rhône-Alpes Rhône-Alpes Rhône Activity type Higher or Secondary Education Establishments Principal investigator Patrick Mehlen (Dr.) Administrative Contact Javier Olaiz (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
