- 1) Molecular Mechanisms of CD95-mediated non-apoptotic signaling
- 2) Role of CD95-mediated non-apoptotic signaling pathways in inflammation (lupus) and oncogenesis (triple negative breast cancer)
- 3) Biological effect of CD95/CD95L inhibitors
CD95 is a death receptor participating in immune homeostasis and elimination of tumor cells. Its cognate ligand, CD95L, is expressed by activated T cells and NK cells to kill infected and transformed cells. This transmembrane ligand (membrane-bound CD95L or m-CD95L) can be cleaved by metalloproteases to generate a soluble ligand (cleaved CD95L or cl-CD95L) that fails to trigger cell death but promotes inflammation in different chronic inflammatory disorders and in patients affected by breast cancer by implementing PI3K, MAPK or NFκB signaling pathways.
The team aims at identifying the molecular mechanisms involved in CD95-mediated non-apoptotic signaling pathways and at characterizing their biological roles in the progression of pathologies such as breast cancers and chronic inflammatory disorders (e.g., systemic lupus erythematosus).
To this end, the team evaluates:
- 1) In a molecular standpoint, the unconventional CD95-mediated cell signaling implemented by cl-CD95L.
- 2) In Human and mouse models, the biological role of this signal at different stages of the pathologies.
Figure 1: cl-CD95L/CD95 interaction leads to the implementation of a unconventional signaling pathway (from Malleter, Cancer res, 2013).
Figure 2: Administration of cl-CD95L in mice xenografted with luminescent triple-negative breast cancer cells enhances the metastatic process.