Transcription factors FOXG1 and Groucho/TLE promote glioblastoma growth

Glioblastoma (GBM) is the most common and deadly malignant brain cancer, with a median survival of less than two years. GBM displays a cellular complexity that includes brain tumour-initiating cells (BTICs), which are considered as potential key targets for GBM therapies. Here we show that the transcription factors FOXG1 and Groucho/TLE are expressed in poorly differentiated astroglial cells in human GBM specimens and in primary cultures of GBM-derived BTICs, where they form a complex. FOXG1 knockdown in BTICs causes downregulation of neural stem/progenitor and proliferation markers, increased replicative senescence, upregulation of astroglial differentiation genes, and decreased BTIC-initiated tumour growth upon intracranial transplantation into host mice. These effects are phenocopied by Groucho/TLE knockdown or dominant-inhibition of the FOXG1:Groucho/TLE complex. These results provide evidence that transcriptional programs regulated by FOXG1 and Groucho/TLE are important for BTIC-initiated brain tumour growth, implicating FOXG1 and Groucho/TLE in GBM tumorigenesis.