Altogether, our results propose that the fine interplay between ASCL1 and its target NDRG1 might serve as potential subgroup-specific targetable vulnerability in GBM; enhancing ASCL1 expression in PN GBMs might reduce tumorigenesis, whereas repressing NDRG1 expression might be actionable to hamper the malignancy of GBM belonging to the MES subgroup.
Importantly, force-expression of Ascl1 was shown to drive proliferative reactive astroglia formed during stroke and glioblastoma stem cells towards neuronal differentiation, and this could potentially diminish CNS damage resulting from their proliferation.
Here, we show that a large subset of patient-derived glioblastoma stem cells (GSCs) express high levels of Achaete-scute homolog 1 (ASCL1), a proneural transcription factor involved in normal neurogenesis.
Our findings demonstrate regulatory connections among ASCL1, Wnt signaling, and collaborating TFs that are essential for the maintenance and tumorigenicity of GBM CSCs.
Several genes associated with primary GBM were overexpressed in CE tumors, whereas ASCL1, which is associated with secondary GBM, was overexpressed in IE tumors.