PO-201 NF1 inhibits glioma cells invasion and reverts mesenchymal transition

Abstract

IntroductionNeurofibromin (NF1), a tumour suppressor and RAS-GTPase activating protein, is one of the highly mutated genes in cancer. Dysregulated NF1 expression promotes tumorigenesis, impairs learning and memory and affects neural development. Loss of NF1 expression is observed in approximately 13% of all glioma and is associated with increased malignancy. Additionally, NF1-loss increases glioma stem cells self-renewal, heightens cell invasion, and promotes mesenchymal transition resulting in enhanced tumour aggressiveness. However, aside from its RAS-GAP function, it is not clear how NF1 mitigate cell invasion and mesenchymal transition. Herein, we show that the leucine-rich domain (LRD) of NF1 plays a role in cell invasion.Material and methodsPatient-derived glioma cells was used in this study. Immunohistochemistry staining was use for assessing proneural and mesenchymal markers expression.Results and discussionsExogenous expression of LRD in NF1-knockdown glioma cells inhibited cell invasion in vitro and in vivo. Using immunohistochemistry staining for cancer stem cell markers associated with proneural (Sox2) and mesenchymal (CD44 and vimentin) subtype of glioblastoma, we found high Sox2 but low vimentin expression in LRD-expressing tumour when compared with the NF1-knockdown tumour.ConclusionOur data suggests that LRD may play a role in reverting mesenchymal GBM to a less invasive and therapy-sensitive subtype.