Chen Alexander, Wang Hannah, Li Xuanwei, Anastasaki Corina, Gutmann David H
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA
Genes Dev. 2025 Jun 2;39(11-12):697-705. doi: 10.1101/gad.352508.124.
The two major genomic alterations in pediatric pilocytic astrocytoma (PA) are loss and rearrangement. Although these molecular changes result in increased MEK activity and tumor growth, it is not clear exactly how MEK controls human neuroglial cell proliferation. Leveraging human-induced pluripotent stem cells harboring these PA-associated alterations, we used a combination of genetic and pharmacological approaches to demonstrate that MEK-regulated cell growth is mediated by β-catenin through independent mechanisms involving IRX2 control of transcription and NPTX1 stabilization of β-catenin protein levels. These results provide new mechanistic insights into MEK regulation of human brain cell function.
小儿毛细胞型星形细胞瘤（PA）的两个主要基因组改变是缺失和重排。尽管这些分子变化导致MEK活性增加和肿瘤生长，但尚不清楚MEK究竟如何控制人类神经胶质细胞增殖。利用携带这些PA相关改变的人诱导多能干细胞，我们结合遗传和药理学方法证明，MEK调节的细胞生长是由β-连环蛋白通过涉及IRX2转录控制和β-连环蛋白蛋白水平NPTX1稳定的独立机制介导的。这些结果为MEK对人脑细胞功能的调节提供了新的机制见解。
