CD95 (also known as Fas) is considered as a death receptor and it belongs to the TNF (tumor necrosis factor) receptor family. Its ligand, CD95L is a transmembrane cytokine (m-CD95L), which can be cleaved by metalloproteases and released in bloodstream as a soluble fragment (cl-CD95L).
While m-CD95L is found at the surface of immune cells (mainly activated T cells and NK cells) where it orchestrates the elimination of transformed/infected cells and the immune contraction, its metalloprotease-cleaved counterpart, namely cl-CD95L (cleaved-CD95L), behaves as a proto-oncogene enhancing the risk of metastatic occurrence in breast cancers.
By ELISA, the amounts of cl-CD95L are found increased in serum of patients suffering from inflammatory disorders such as lupus or cancers such as triple negative breast cancer as compared to healthy subjects. More importantly, the concentrations of cl-CD95L in these pathologies are associated with the disease progression.
The DR@TE Team goals are to decipher i) how CD95 switches from implementing cell death to non-apoptotic signaling pathways (and vice versa) and ii) what are the molecular mechanisms induced by this ligand in triple negative breast cancer women and involved in promoting metastatic dissemination.
Figure 1: Luciferase-expressing MDA-MB-231 cells were orthotopically injected in NOD/SCID/γc null mice. Then, cl-CD95L (10 μg/kg) or vehicle was repeatedly injected and metastatic dissemination of TNBC cells was evaluated by bioluminescence imaging (BLI) at day 21. Black arrows depict mice showing luciferase-expressing MDA-MB-231 spreading (Coll. Dr Y. Collette, Marseille).