MEF Promotes Stemness in the Pathogenesis of Gliomas
A partir de données issues du projet "The Cancer Genome Atlas", cette étude menée in vitro met en évidence un mécanisme par lequel, en activant le gène Sox2, le facteur de transcription MEF favorise la prolifération de cellules souches de gliomes
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. º Human and mouse glioblastoma samples express high levels of MEF gene º Lack of MEF in mouse models impairs glioma formation and aggressiveness º MEF promotes stem cell traits of mouse primary brain cells and human glioma cells º Sox2 gene expression is directly regulated by MEF The transcription factor MEF promotes stem-cell-like characteristics in gliomagenesis through activation of Sox2.
http://linkinghub.elsevier.com/retrieve/pii/S1934590912005784