期刊
ELIFE
卷 10, 期 -, 页码 -出版社
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.64846
关键词
-
类别
资金
- La Caixa Foundation
- Berlin School of Integrative Oncology, Charite - Universitatsmedizin Berlin
- MDC [VH-NG-1153]
- European Research Council [714922]
- Marie CurieInternational re-integration Grants [268303]
- Instituto de Salud Carlos III [PI13/01028]
- Seve Ballesteros Foundation
- Berlin School of Integrative Oncology
- European Research Council (ERC) [714922] Funding Source: European Research Council (ERC)
The study identified FOSL1 as a key regulator of the mesenchymal subtype in GBM, with NF1 gene playing a role in GBM mesenchymal transformation through modulation of FOSL1 expression. Depletion of FOSL1 in NF1-mutant human BTSCs and Kras-mutant mouse neural stem cells results in loss of the mesenchymal gene signature.
The molecular basis underlying glioblastoma (GBM) heterogeneity and plasticity is not fully understood. Using transcriptomic data of human patient-derived brain tumor stem cell lines (BTSCs), classified based on GBM-intrinsic signatures, we identify the AP-1 transcription factor FOSL1 as a key regulator of the mesenchymal (MES) subtype. We provide a mechanistic basis to the role of the neurofibromatosis type 1 gene (NF1), a negative regulator of the RAS/MAPK pathway, in GBM mesenchymal transformation through the modulation of FOSL1 expression. Depletion of FOSL1 in NF1-mutant human BTSCs and Kras-mutant mouse neural stem cells results in loss of the mesenchymal gene signature and reduction in stem cell properties and in vivo tumorigenic potential. Our data demonstrate that FOSL1 controls GBM plasticity and aggressiveness in response to NF1 alterations.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据