胶质瘤
SOX2
生物
JAG1
白质
转录因子
Notch信号通路
癌症研究
硫氧化物9
表型
干细胞
细胞生物学
信号转导
医学
遗传学
基因
磁共振成像
放射科
作者
Jun Wang,Senlin Xu,Jiang‐Jie Duan,Yi Liang,Yufeng Guo,Yu Shi,Lin Li,Zeyu Yang,Xuemei Liao,Jiao Cai,Yanqi Zhang,Hualiang Xiao,Li Yin,Hao Wu,Jingna Zhang,Shengqing Lv,Qingkai Yang,Xiaojun Yang,Tao Jiang,Xia Zhang,Xiu‐Wu Bian,Shi‐Cang Yu
标识
DOI:10.1038/s41593-018-0285-z
摘要
Early invasive growth along specific anatomical structures, especially the white matter tract, is regarded as one of the main causes of poor therapeutic outcome of people with gliomas. We show that some glioma stem cells (GSCs) are preferentially located along white matter tracts, which exhibit a demyelinated phenotype, at the invasive frontier of glioma tissues. These GSCs are CD133+Notch1+, whereas the nerve fibers express the Notch ligand Jagged1. The Notch-induced transcription factor Sox9 promotes the transcription of SOX2 and the methylation level of the NOTCH1 promoter is attenuated by the upregulation of SOX2 to reinforce NOTCH1 expression in GSCs. This positive-feedback loop in a cohort of glioma subjects is correlated with a poor prognosis. Inhibition of Notch signaling attenuates the white-matter-tract tropism of GSCs. These findings provide evidence indicating that the NOTCH1-SOX2 positive-feedback loop controls GSC invasion along white matter tracts.
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