Fiche publication
Date publication
septembre 2016
Journal
Oncotarget
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BAGNARD Dominique
,
Dr GOETZ Jacky
,
Dr OREND Gertraud
Tous les auteurs :
Jacob L, Sawma P, Garnier N, Meyer LA, Fritz J, Hussenet T, Spenlé C, Goetz J, Vermot J, Fernandez A, Baumlin N, Aci-Sèche S, Orend G, Roussel G, Crémel G, Genest M, Hubert P, Bagnard D
Lien Pubmed
Résumé
The neuropilin-plexin receptor complex regulates tumor cell migration and proliferation and thus is an interesting therapeutic target. High expression of neuropilin-1 is indeed associated with a bad prognosis in glioma patients. Q-RTPCR and tissue-array analyses showed here that Plexin-A1 is highly expressed in glioblastoma and that the highest level of expression correlates with the worse survival of patients. We next identified a developmental and tumor-associated pro-angiogenic role of Plexin-A1. Hence, by using molecular simulations and a two-hybrid like assay in parallel with biochemical and cellular assays we developed a specific Plexin-A1 peptidic antagonist disrupting transmembrane domain-mediated oligomerization of the receptor and subsequent signaling and functional activity. We found that this peptide exhibits anti-tumor activity in vivo on different human glioblastoma models including glioma cancer stem cells. Thus, screening Plexin-A1 expression and targeting Plexin-A1 in glioblastoma patients exhibit diagnostic and therapeutic value.
Référence
Oncotarget. 2016 09;7(36):57851-57865
