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    Friday Séminaire 25/09/2015

    Friday Séminaire 25/09/2015

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    Séminaire de Raphaël Bergès

    INSERM UMR911, Centre de Recherche en Oncologie biologique et Oncopharmacologie.

    Le 25 septembre 2015

    Un séminaire sera donné par Raphaël Bergès, INSERM UMR911, Centre de Recherche en Oncologie biologique et Oncopharmacologie, Marseille.

     

    «End-binding 1 protein overexpression correlates with glioblastoma progression and sensitizes to Vinca-alkaloids in vitro and in vivo»



    Les étudiants souhaitant assister à la conférence doivent s'inscrire au préalable avant le jeudi  24 septembre 12h00 dans la limite des places disponibles auprès de : secr-inserm-angers @ contact.univ-angers.fr en communiquant leur numéro de carte étudiante.

    Pour que la participation au séminaire soit validante, il est impératif que les étudiants émargent la feuille de présence.

    Pour rappel, les étudiants non inscrits ne seront pas acceptés.


    12h00 - 13h00
    CHU Angers - Bâtiment IBS-IRIS – Salle de conférence RDC

     secr-inserm-angers@contact.univ-angers.fr


    End-binding 1 protein (EB1) is a key player in the regulation of microtubule (MT) dynamics. In the present study we investigated the role of EB1 in glioblastoma (GBM) tumor progression and its potential predictive role for response to Vinca-alkaloid chemotherapy. Immunohistological analysis of the 109 human GBM cases revealed that EB1 overexpression correlated with poor outcome including progression-free survival and overall survival. In order to decipher the implication of EB1 in GBM disease, its expression was knocked down or up-regulated in several human U87 GBM clones. Downregulation of EB1 by shRNA inhibited cell migration and proliferation in vitro. Conversely, EB1 overexpression promoted them and accelerated tumor growth in orthotopically-transplanted nude mice. Furthermore, EB1 expression was evaluated in stem-like GBM6 and GBM9 cells isolated from two GBM patients. GBM6, that display in vivo a higher tumorigenicity with a more infiltrative pattern of migration than GBM9, largely overexpressed EB1 as compared to GBM9. GBM6 showed strong and EB1-dependent migratory potential. The predictive role of EB1 in the response of GBM cells to Vinca-alkaloid treatment was investigated. Vinflunine (VFL) and vincristine (VCR) increased survival of EB1-overexpressing U87 bearing mice as compared to control. Besides, VFL and VCR were more effective to inhibit cell migration and proliferation in EB1-overexpressing clones than in controls. MT dynamics was increased in EB1 overexpressing U87 cells. The cellular sensitization to Vinca-alkaloids was linked to a stronger alteration of MT dynamic instability in these cells, thus inhibiting the increase induced by EB1 overexpression. Altogether, our results show that EB1 expression level has a prognostic value in GBM, and that Vinca-alkaloid chemotherapy could improve the treatment of GBM patients with EB1-overexpressing tumor.