Characterization of a FOXG1:TLE1 transcriptional network in glioblastoma-initiating cells

Rola Dali, Federica Verginelli, Albena Pramatarova, Robert Sladek, Stefano Stifani

Research output: Contribution to journalArticle

Abstract

Glioblastoma (GBM) is the most common and deadly malignant brain cancer of glial cell origin, with a median patient survival of less than 20 months. Transcription factors FOXG1 and TLE1 promote GBM propagation by supporting maintenance of brain tumour-initiating cells (BTICs) with stem-like properties. Here, we characterize FOXG1 and TLE1 target genes in GBM patient-derived BTICs using ChIP-Seq and RNA-Seq approaches. These studies identify 150 direct FOXG1 targets, several of which are also TLE1 targets, involved in cell proliferation, differentiation, survival, chemotaxis and angiogenesis. Negative regulators of NOTCH signalling, including CHAC1, are among the transcriptional repression targets of FOXG1:TLE1 complexes, suggesting a crosstalk between FOXG1:TLE1 and NOTCH-mediated pathways in GBM. These results provide previously unavailable insight into the transcriptional programs underlying the tumour-promoting functions of FOXG1:TLE1 in GBM.

Original languageEnglish
Pages (from-to)775-787
Number of pages13
JournalMolecular Oncology
Volume12
Issue number6
DOIs
Publication statusPublished - Jun 1 2018

    Fingerprint

Keywords

  • CHAC1
  • ChIP-Seq/RNA-Seq
  • FOXG1
  • glioblastoma
  • Groucho/transducin-like Enhancer of split
  • NOTCH

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cancer Research

Cite this