title: End-binding 1 protein overexpression correlates with glioblastoma progression and sensitizes to Vinca-alkaloids in vitro and in vivo.
abstract: End-binding 1 protein (EB1) is a key player in the regulation of microtubule (MT) dynamics. Here, 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. 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 was largely overexpressed in stem-like GBM6 that display in vivo a higher tumorigenicity with a more infiltrative pattern of migration than stem-like GBM9. GBM6 showed strong and EB1-dependent migratory potential. The predictive role of EB1 in the response of GBM cells to chemotherapy was investigated. Vinflunine and vincristine increased survival of EB1-overexpressing U87 bearing mice and were more effective to inhibit cell migration and proliferation in EB1-overexpressing clones than in controls. Vinca inhibited the increase of MT growth rate and growth length 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.
authors.affiliation: Aix-Marseille Université, INSERM, CRO2 UMR_S 911, Marseille 13385, France.
authors.forename: Raphael
authors.initials: R
authors.lastname: Berges
authors.affiliation: Aix-Marseille Université, INSERM, CRO2 UMR_S 911, Marseille 13385, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Baeza-Kallee
authors.affiliation: Aix-Marseille Université, INSERM, CRO2 UMR_S 911, Marseille 13385, France. APHM, CHU Timone, Marseille 13385, France.
authors.forename: Emeline
authors.initials: E
authors.lastname: Tabouret
authors.affiliation: Aix-Marseille Université, INSERM, CRO2 UMR_S 911, Marseille 13385, France. APHM, CHU Timone, Marseille 13385, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Chinot
authors.affiliation: Aix-Marseille Université, INSERM, CRO2 UMR_S 911, Marseille 13385, France. APHM, CHU Timone, Marseille 13385, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Petit
authors.affiliation: Centre de Recherche d'Oncologie Expérimentale, Institut de Recherche Pierre Fabre, Toulouse, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Kruczynski
authors.affiliation: Aix-Marseille Université, INSERM, CRO2 UMR_S 911, Marseille 13385, France. APHM, CHU Timone, Marseille 13385, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Figarella-Branger
authors.affiliation: Aix-Marseille Université, INSERM, CRO2 UMR_S 911, Marseille 13385, France. APHM, CHU Timone, Marseille 13385, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Honore
authors.affiliation: Aix-Marseille Université, INSERM, CRO2 UMR_S 911, Marseille 13385, France. APHM, CHU Timone, Marseille 13385, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Braguer
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D014747:Vinblastine / Q000031:analogs & derivatives / Q000494:pharmacology; D014748:Vinca Alkaloids / Q000494:pharmacology*; D014750:Vincristine / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: C500985:MAPRE1 protein, human; D008869:Microtubule-Associated Proteins; D014748:Vinca Alkaloids; C111217:vinflunine; D014750:Vincristine; D014747:Vinblastine