Cell death signalling

Activation of proapoptotic receptors by recombinant TRAIL or agonistic antibodies is currently undergoing clinical trials as a potential therapeutic strategy against solid and hematological tumours. However, there are still many uncertainties regarding the resistance of nontumour cells to TRAIL. Furthermore, a number of studies suggest that primary tumours are also resistant to TRAIL. We are involved in the study of the mechanisms controlling the resistance of normal breast epithelial cells to the apoptotic ligand TRAIL. We also intend to define the molecular basis of the regulation of TRAIL sensitivity during the epithelial to mesenchymal transition (EMT) in cancer cells. Our interest is also to characterize the role of the TRAIL system in cell death decisions after metabolic stress in tumor cells and to decipher the mechanisms of the adaptive response in tumors that allows tumor cells to escape from metabolic stress-induced apoptosis.