Journal
CELL STEM CELL
Volume 11, Issue 6, Pages 836-844Publisher
CELL PRESS
DOI: 10.1016/j.stem.2012.09.012
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Funding
- National Brain Tumor Foundation [RO1-DK52208, U54CAI43798, UO1CA141502, RO1CA100688]
- Brain Tumor Center of Memorial Sloan-Kettering Cancer Center
- Rottendorf Foundation, Ennigerloh, Germany
- Gerhard Domagk Scholarship Program, Greifswald, Germany
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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.
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