DOCK4 PROMOTES LOSS OF PROLIFERATION IN GLIOBLASTOMA PROGENITOR CELLS THROUGH NUCLEAR BETA-CATENIN ACCUMULATION AND SUBSEQUENT miR-302-367 CLUSTER EXPRESSION

DOCK4 PROMOTES LOSS OF PROLIFERATION IN GLIOBLASTOMA PROGENITOR CELLS THROUGH NUCLEAR BETA-CATENIN ACCUMULATION AND SUBSEQUENT miR-302-367 CLUSTER EXPRESSION

11^th International Conference on Cancer Stem Cells and Oncology Research
June 11-13, 2018 | Dublin, Ireland

Thierry Virolle , David Nicolas Debruyne, Laurent Turchi, Fanny Burel-Vandenbos, Mohamed Fareh, FabienAlmairac,Virginie Virolle, Dominique Figarella-Branger, Nathalie Baeza-Kallee, Patricia Lagadec, Valerie kubiniek, Philippe Paquis, Denys Fontaine, Marie-Pierre Junier and Herve Chneiweiss

Universite Cote d’Azur, France CNRS, France Inserm, France Service d’Anatomopathologie, Hopital Pasteur, France Service de Neurchirurgie, Hopital Pasteur, France Aix Marseille Universite, France INSERM, France Departement de Pathology, CHU de la Timone, France Laboratory of Solid Tumors Genetics, University Hospital of Nice, France CNRS Neuroscience Paris Seine – IBPS, France Inserm, France University Pierre and Marie Curie, Neuroscience Paris Seine – IBPS, France

Scientific Tracks Abstracts : J Med Oncl Ther

Abstract:

Glioblastomas (GBM) are lethal primitive brain tumours characterized by a strong intra-tumour heterogeneity. We observed in GBM tissues the coexistence of functionally divergent micro-territories either enriched in more differentiated and non-mitotic cells or in mitotic undifferentiated OLIG2 positive cells while sharing similar genomic abnormalities. Understanding the formation of such functionally divergent micro-territories in glioblastomas (GBM) is essential to comprehend GBM biogenesis, plasticity and to develop therapies. Here we report an unexpected anti-proliferative role of beta-catenin in nonmitotic differentiated GBM cells. By cell type specific stimulation of miR-302, which directly represses cyclin D1 and stemness features, betacatenin is capable to change its known proliferative function. Nuclear beta-catenin accumulation in non-mitotic cells is due to a feed forward mechanism between DOCK4 and beta-catenin, allowed by increased GSK3-beta activity. DOCK4 over expression suppresses selfrenewal and tumorigenicity of GBM stem-like cells. Accordingly in the frame of GBM median of survival, increased level of DOCK4 predicts improved patient survival.

Biography:

Thierry Virolle is a Research Director (permanent position) at Institut National de la Santé et de la Recherche Médicale (INSERM), Head of the Team Cancer Stem Cell Plasticity and Functional intra-tumor Heterogeneity at the Institute of Biologie Valrose (iBV). He is Co-Founder of the French National Sud Cancer Stem Cell Network, SUNRiSE dedicated to the study of cancer stem cell.

Email:Virolle@unice.fr

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