GNT-V TARGETING BY THE PHOSTINE PST3.1a INHIBITS GBM STEM CELLS STEMNESS AND THEIR IN VIVO PROLIFERATION AND INVASIVENESS
Tumor progression has been shown to be correlated with the expression of tri- and tetra-antennary β1,6-N-acetylglucosamine-bearing N-glycans. Glioblastoma were reported to express highly variable amounts of both GnT-III and GnT-V mRNA suggesting an important physiological role in maintaining the balance of these exclusive enzymatic activities . We demonstrated that PST3.1a alters the β1,4-GlcNAc and β1,6-GlcNAc N-glycans of GBM stem cells (GBMSC), by inhibiting the GnT-V enzymatic activity and reducing GnT-III expression. In a second step physiological and signaling effects of PST3.1a were analyzed on GBMSC cultivated either in proliferation or differentiation culture media. In a third step the in vivo pharmacological activity was evaluated in a subcutaneous model using the SNB75 cell line and in orthotopic models using the GBMSC Gli4 and GliT. Finally we showed that mitochondrial gene expressions were negatively correlated with PsT3.1a cytotoxic activity against the NCI-60 cancer cell lines panel
Date:
2 March 2016, 11:00 (Wednesday, 7th week, Hilary 2016)
Venue:
Rodney Porter Building, off South Parks Road OX1 3QU
Venue Details:
Howard Schneidermann Room
Speaker:
Professor Norbert Bakalara (The Institute for Neurosciences of Montpellier)
Organising department:
Department of Biochemistry
Organiser:
Stephen Woodhouse (University of Oxford, Department of Biochemistry)
Organiser contact email address:
stephen.woodhouse@bioch.ox.ac.uk
Part of:
Infection and Disease Processes Seminar Series
Booking required?:
Not required
Audience:
Members of the University only
Editor:
Stephen Woodhouse
