RND1 regulates migration of human glioblastoma stem-like cells according to their anatomical localization and defines a prognostic signature in glioblastoma.
Fiche publication
Date publication
septembre 2018
Journal
Oncotarget
Auteurs
Membres identifiés du Cancéropôle Est :
Pr LEHMANN Maxime
Tous les auteurs :
Boyrie S, Delmas C, Lemarié A, Lubrano V, Dahan P, Malric L, Luis J, Gilhodes J, Tosolini M, Mouly L, Lehmann M, Toulas C, Cohen-Jonathan Moyal E, Monferran S
Lien Pubmed
Résumé
Despite post-operative radio-chemotherapy, glioblastoma systematically locally recurs. Tumors contacting the periventricular zone (PVZ) show earlier and more distant relapses than tumors not contacting the PVZ. Since glioblastoma stem-like cells (GSCs) have been proposed to play a major role in glioblastoma recurrence, we decided to test whether GSC migration properties could be different according to their anatomical location (PVZ+/PVZ-). For that purpose, we established paired cultures of GSCs from the cortical area (CT) and the PVZ of glioblastoma patient tumors. We demonstrated that PVZ GSCs possess higher migration and invasion capacities than CT GSCs. We highlighted specific transcriptomic profiles in PVZ versus CT populations and identified a down-regulation of the RhoGTPase, in PVZ GSCs compared to CT GSCs. Overexpression of RND1, dramatically inhibited PVZ GSC migration and conversely, downregulation of increased CT GSC migration. Additionally, transcriptomic analyses also revealed a down-regulation of in glioblastoma compared to normal brain. Using the glioblastoma TCGA database, low levels of were also shown to correlate with a decreased overall survival of patients. Finally, based on signaling pathways activated in patients with low levels of , we identified an signature of six genes (MET, LAMC1, ITGA5, COL5A1, COL3A1, COL1A2) that is an independent prognostic factor in glioblastoma. These findings contribute to explain the shorter time to progression of patients with PVZ involvement and, point out genes that establish the signature as key targets genes to impede tumor relapse after treatment.
Mots clés
RND1, glioblastoma stem-like cells, migration, periventricular zone, prognostic signature
Référence
Oncotarget. 2018 Sep 18;9(73):33788-33803