期刊
NATURE COMMUNICATIONS
卷 4, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms3956
关键词
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资金
- Banting and Best CGS Master's Award
- Fonds de la Recherche en Sante du Quebec
- Vanier Canada CGS
- Canadian Institutes of Health Research [MOP-13957, IC1-115711]
- Cancer Research Society
- Fondo per gli Investimenti di Ricerca di Base [FIRB-RBIN062YH4]
- Alberta Innovates [201201230] Funding Source: researchfish
Glioblastoma (GBM) is the most common and deadly malignant brain cancer, with a median survival of <2 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 after 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 programmes regulated by FOXG1 and Groucho/TLE are important for BTIC-initiated brain tumour growth, implicating FOXG1 and Groucho/TLE in GBM tumourigenesis.
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