title: Transcription factors FOXG1 and Groucho/TLE promote glioblastoma growth.
abstract: 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.
authors.affiliation: 1] Centre for Neuronal Survival, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada H3A 2B4 [2].
authors.forename: Federica
authors.initials: F
authors.lastname: Verginelli
authors.affiliation: 1] Centre for Neuronal Survival, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada H3A 2B4 [2] [3].
authors.forename: Alessandro
authors.initials: A
authors.lastname: Perin
authors.affiliation: Centre for Neuronal Survival, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada H3A 2B4.
authors.forename: Rola
authors.initials: R
authors.lastname: Dali
authors.affiliation: Centre for Neuronal Survival, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada H3A 2B4.
authors.forename: Karen H
authors.initials: KH
authors.lastname: Fung
authors.affiliation: Centre for Neuronal Survival, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada H3A 2B4.
authors.forename: Rita
authors.initials: R
authors.lastname: Lo
authors.affiliation: Department of Neurosurgery, Treviso Hospital, University of Padova, Padova 31100, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Longatti
authors.affiliation: Department of Neuropathology, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada H3A 2B4.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Guiot
authors.affiliation: Brain Tumour Research Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada H3A 2B4.
authors.forename: Rolando F
authors.initials: RF
authors.lastname: Del Maestro
authors.affiliation: Department of Pathology, Treviso Hospital, University of Padova, Padova 31100, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Institute of Genetics and Biophysics, Adriano Buzzati Traverso, Napoli 80131, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: di Porzio
authors.affiliation: Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
authors.forename: Owen
authors.initials: O
authors.lastname: Stechishin
authors.affiliation: Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
authors.forename: Samuel
authors.initials: S
authors.lastname: Weiss
authors.affiliation: Centre for Neuronal Survival, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada H3A 2B4.
authors.forename: Stefano
authors.initials: S
authors.lastname: Stifani
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056970:Co-Repressor Proteins; D051858:Forkhead Transcription Factors / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005909:Glioblastoma / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D009419:Nerve Tissue Proteins / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D014157:Transcription Factors / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D056970:Co-Repressor Proteins; C090173:FOXG1 protein, human; D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins; C530203:Tle6 protein, human; D014157:Transcription Factors