The Marseille Cancer Research Center celebrates its 50th anniversary ! -
We are investigating novel pathways controlling cell signaling and cell-cell communication and exploring their potential benefit for the cancer field. We concentrate our studies on scaffold proteins (heparan sulfate proteoglycans and PDZ proteins) and signaling lipids (phosphoinositides) that are important molecules for the spatio-temporal organisation of cell signaling.
In particular we study their effect on the half-life of signaling receptors, their role in cell-cell communication and their impact on nuclear processes. We thereby hope to pave the way for innovative therapeutic approaches.
In the last years, we published four main studies establishing (i) the syndecan-syntenin crosstalk with tetraspanins, a family of transmembrane proteins broadly used as extracellular vesicle (EV) markers; (ii) the role of syndecan-syntenin in the uptake of exosomes (small EVs) and in the viral transduction; (iii) that SRC supports non-autonomous cell signaling by directly controlling syndecan- syntenin exosome biogenesis and cargo-loading and (iv) that it is possible to develop selective inhibitors of syndecan-syntenin interactions and that those can modulate the oncogenic composition of exosomes.
We currently have three main papers in submission/revision establishing (i) the role of the ESCRT-I component MVB12B in the production of small EV; (ii) that downregulation of stromal syntenin sustains AML development; and (iii) that many members of the PDZ protein family interact with syndecans and tetraspanins to modulate the production, composition and/or uptake of EVs. Besides focusing on the biology of EV and on the mechanisms that support their biogenesis and signaling functions, we more recently launched collaborative projects aiming at exploiting these insights for therapeutic purposes. Specifically, in collaboration with several local and international teams, we intend engineering ‘therapeutic’ EVs capable of targeting and reprograming tumor cells in pancreatic cancer (PDAC).
For the future projects, we aim to conduct three lines of research which are to (A) understand the role of metalloproteases in the biology of syndecan-syntenin EV; (B) evaluate the role of syndecan-syntenin in tumor- bone relationships and (C) obtain the proof of concept that rationally designed EV (based on synthetic biology and our fundamental insight of the molecular mechanisms governing EV-signaling) can improve precision medicine.
Team publications
Leblanc R, Ghossoub R, Goubard A, Castellano R, Fares J, Camoin L, Audebert S, Balzano M, Bou-Tayeh B, Fauriat C, Vey N, Garciaz S, Borg JP, Collette Y, Aurrand-Lions M, David G, Zimmermann P
Castro-Cruz M, Hyka L, Daaboul G, Leblanc R, Meeussen S, Lembo F, Oris A, Van Herck L, Granjeaud S, David G, Zimmermann P
Hoffer L, Garcia M, Leblanc R, Feracci M, Betzi S, Ben Yaala K, Daulat AM, Zimmermann P, Roche P, Barral K, Morelli X
