MEF promotes stemness in the pathogenesis of gliomas

Cell Stem Cell. 2012 Dec 7;11(6):836-44. doi: 10.1016/j.stem.2012.09.012.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology*
  • Humans
  • Mice
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / pathology
  • SOXB1 Transcription Factors / metabolism
  • Spheroids, Cellular / metabolism
  • Spheroids, Cellular / pathology
  • Tissue Culture Techniques
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • ELF4 protein, human
  • Elf4 protein, mouse
  • SOXB1 Transcription Factors
  • Transcription Factors