Team description

CD95 (also known as Fas) is considered as a death receptor that belongs to the TNF receptor family. Its ligand, CD95L is a transmembrane cytokine (m-CD95L), which can be cleaved by metalloproteases and released in the blood stream (cl-CD95L). While m-CD95L is found at the surface of immune cells where it orchestrates the elimination of transformed and infected cells, the patho-physiological role(s) of cl-CD95L remains to be elucidated. Upon CD95L binding, CD95 recruits different proteins (i.e, FADD, caspase-8/10) resulting in the formation of a complex designated Death Inducing Signaling Complex (DISC). Ultimately, DISC triggers cell death. We recently demonstrated that in contrast to m-CD95L, cl-CD95L induces the formation of a molecular complex devoid of FADD and caspase-8/10 that we called Motility Inducing Signaling Complex (MISC). MISC elicits phosphoinositide-3 kinase (PI3K) activation and promotes cell migration. The pathophysiological roles of MISC and cl-CD95L have to be elucidated. Our group tries to identify the orderly sequence of events leading to DISC or MISC formation in normal cells and to understand how these events can be overridden by malignant cells.

Role in the network

This team will in be in charge of the characterization of the molecular mechanisms linking CD95 engagement to the activation of Orai1 and the subsequent metastatic dissemination of cancer cells.

Involvement in tasks 1

VALORIZATIONS/COLLABORATIONS

Publications / Patents

Patents

2015. EP15305606.4 -Methods and pharmaceutical compositions for the treatmentof th17 mediated diseases

2014. EP14305570- Polypeptides and uses thereof for reducing CD95-mediated cell motility

2014. EP14305877-Methods and pharmaceutical compositions for reducing CD95-mediated cell motility

2014.WO2014118317-Methods for predicting and preventing metastasis in triple negative breast cancers

2014.EP14305019- Methods and Pharmaceutical compositions for preventing or reducing metastatic dissemination

Team publication

Fouqué A, Delalande O, Jean M, Castellano R, Josselin E, Malleter M, Shoji KF, Hung MD, Rampanarivo H, Collette Y, van de Weghe P, Legembre P.J Med Chem. 2015 Aug 27;58(16):6559-73.

Fouqué A, Debure L, Legembre P.BBA-Reviews On Cancer. 2014. Review.

Edmond V, Dufour F, Poiroux G, Shoji K, Malleter M, Fouqué A, Tauzin S, Rimokh R, Sergent O, Penna A, Dupuy A, Levade T, Theret N, Micheau O, Ségui B, Legembre P.Oncogene. 2014.

Malleter M, Tauzin S, Bessede A, Castellano R, Goubard A, Godey F, Leveque J, Jezequel P, Campion L, Campone M, Ducret T, Macgrogan G, Debure L, Collette Y, Vacher P, Legembre P.Cancer Res.2013.

Khadra N, Bresson-Bepoldin L, Penna A, Chaigne-Delalande B, Ségui B, Levade T, Vacher AM, Reiffers J, Ducret T, Moreau JF, Cahalan MD, Vacher P, Legembre P.PNAS. 2011.

Tauzin S, Chaigne-Delalande B, Selva E, Khadra N, Daburon S, Contin-Bordes C, Blanco P, Le Seyec J, Ducret T, Counillon L, Moreau JF, Hofman P, Vacher P and Legembre P.PLoS Biology. 2011.