title: MEF promotes stemness in the pathogenesis of gliomas.
abstract: High-grade gliomas are aggressive and uniformly fatal tumors, composed of a heterogeneous population of cells that include many with stem-cell-like properties. The acquisition of stem-like traits might contribute to glioma initiation, growth, and recurrence. Here we investigated the role of the transcription factor myeloid Elf-1 like factor (MEF, also known as ELF4) in gliomas. We found that MEF is highly expressed in both human and mouse glioblastomas and its absence impairs gliomagenesis in a PDGF-driven glioma mouse model. We show that modulation of MEF levels in both mouse neural stem cells and human glioblastoma cells has a significant impact on neurosphere formation. Moreover, we identify Sox2 as a direct downstream target of MEF. Taken together, our studies implicate MEF as a previously unrecognized gatekeeper gene in gliomagenesis that promotes stem cell characteristics through Sox2 activation.
authors.affiliation: Cancer Biology and Genetics Program, Azienda Ospedaliera Universitaria Integrata, 37134 Verona, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Bazzoli
authors.forename: Teodoro
authors.initials: T
authors.lastname: Pulvirenti
authors.forename: Moritz C
authors.initials: MC
authors.lastname: Oberstadt
authors.forename: Fabiana
authors.initials: F
authors.lastname: Perna
authors.forename: Boyoung
authors.initials: B
authors.lastname: Wee
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Schultz
authors.forename: Jason T
authors.initials: JT
authors.lastname: Huse
authors.forename: Elena I
authors.initials: EI
authors.lastname: Fomchenko
authors.forename: Francesca
authors.initials: F
authors.lastname: Voza
authors.forename: Viviane
authors.initials: V
authors.lastname: Tabar
authors.forename: Cameron W
authors.initials: CW
authors.lastname: Brennan
authors.forename: Lisa M
authors.initials: LM
authors.lastname: DeAngelis
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Nimer
authors.forename: Eric C
authors.initials: EC
authors.lastname: Holland
authors.forename: Massimo
authors.initials: M
authors.lastname: Squatrito
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology; D046509:Tissue Culture Techniques; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C111931:ELF4 protein, human; C491779:Elf4 protein, mouse; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors