Abstract B14: Wnt signaling circuits in glioblastoma multiforme

Glioblastoma multiforme (GBM) is the most common malignant tumour in the central nervous system with a prevalence of 2-3 cases per 100 000 people. Although the standard treatment of surgery, chemotherapy and radiotherapy improve survival, the median survival continues to remain at only 15 months with a 5-year survival rate of under 10%. Glioma neural stem-like (GNS) cells have been identified in GBM and have the capability of regenerating the tumour. Treatment strategies that target the majority of the tumour may be incapable of also targeting GNS cells and thus characterization of GNS cells may provide insight into additional treatment options. The Wnt signalling pathway has been linked to several cancers including GBM. Wnt signalling involves the secretion of Wnt ligand proteins that bind to specific Frizzled (FZD) receptor complexes on the cell surface of Wnt-responding cells to activate intracellular signalling cascades. The transcriptional and epigenetic regulation in GNS cells is the focus of several recent studies. The transcription factor ASCL1 was identified to be overexpressed and to lead to Wnt signalling activation by repressing Dickkopf (DKK1, Wnt inhibitor). Using microarray data we analyzed the expression of FZD receptors and Wnt target genes in over 50 primary GNS cell lines cultured in serum free conditions in order to maintain the GIC population and identified a subgroup of glioma lines with activated Wnt signalling. To determine the requirement of autocrine...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Signaling Pathways: Wnt: Poster Presentations - Proffered Abstracts Source Type: research