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CANCER STEM CELLS AND
ONCOLOGY RESEARCH
11th International Conference on
Journal of Medical Oncology and Therapeutics | Volume 3
Thierry Virolle et al., J Med Oncl Ther 2018, Volume 3
DOCK4 PROMOTES LOSS OF
PROLIFERATION IN GLIOBLASTOMA
PROGENITOR CELLS THROUGH
NUCLEAR BETA-CATENIN
ACCUMULATION AND SUBSEQUENT
miR-302-367 CLUSTER EXPRESSION
Thierry Virolle 1,2,3, David Nicolas Debruyne1,2,3 , Laurent
Turchi1,2,3,5, Fanny Burel-Vandenbos1,2,3,4, Mohamed Fareh1,2,3 ,
FabienAlmairac1,2,3,Virginie Virolle1,2,3 , Dominique Figarel-
la-Branger6,7,8, Nathalie Baeza-Kallee6,7, Patricia Lagadec1,2,3 ,
Valérie kubiniek9, Philippe Paquis1,2,3,5, Denys Fontaine5,
Marie-Pierre Junier10,11,12 and Hervé Chneiweiss 10,11,12
1Université Côte d’Azur, France
2CNRS, France
3Inserm, France
4Service d’Anatomopathologie, Hôpital Pasteur, France
5Service de Neurchirurgie, Hôpital Pasteur, France
6Aix Marseille Université, France
7INSERM, France
8Departement de Pathology, CHU de la Timone, France
9Laboratory of Solid Tumors Genetics, University Hospital of Nice, France
10CNRS Neuroscience Paris Seine – IBPS, France
11Inserm, France
12University Pierre and Marie Curie, Neuroscience Paris Seine – IBPS, France
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 non-
mitotic differentiated GBM cells. By cell type specific stimulation of
miR-302, which directly represses cyclin D1 and stemness features, beta-
catenin 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.
Thierry Virolle is a Research Director (perma-
nent position) at Institut National de la Santé et
de la Recherche Médicale (INSERM), Head of
the Team Cancer Stem Cell Plasticity and Func-
tional intra-tumor Heterogeneity at the Institute
of Biologie Valrose (iBV). He is Co-Founder of
the French National Sud Cancer Stem Cell Net-
work, SUNRiSE dedicated to the study of cancer
stem cell.
BIOGRAPHY