Cancer Biology and Genetics Program, Azienda Ospedaliera Universitaria Integrata, 37134 Verona, Italy.
Cell Stem Cell. 2012 Dec 7;11(6):836-44. doi: 10.1016/j.stem.2012.09.012.
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.
高级别神经胶质瘤是侵袭性和普遍致命的肿瘤，由多种具有干细胞样特性的细胞组成。获得干细胞样特征可能有助于神经胶质瘤的发生、生长和复发。在这里，我们研究了转录因子髓样 Elf-1 样因子 (MEF，也称为 ELF4) 在神经胶质瘤中的作用。我们发现 MEF 在人和小鼠的神经胶质瘤中均高度表达，其缺失会损害 PDGF 驱动的神经胶质瘤小鼠模型中的神经胶质瘤发生。我们表明，MEF 水平在小鼠神经干细胞和人神经胶质瘤细胞中的调节对神经球形成有显著影响。此外，我们鉴定出 Sox2 是 MEF 的直接下游靶标。总之，我们的研究表明 MEF 是神经胶质瘤发生中的一个以前未被识别的关键基因，通过 Sox2 激活促进干细胞特征。
