IKK/NF-κB signaling contributes to glioblastoma stem cell maintenance.
IKK/NF-κB signaling contributes to glioblastoma stem cell maintenance.
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DOI：
10.18632/oncotarget.12507
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发表时间：
2016-10-25
期刊：
影响因子：
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通讯作者：
Baldwin AS
中科院分区：
文献类型：
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作者：
Rinkenbaugh AL;Cogswell PC;Calamini B;Dunn DE;Persson AI;Weiss WA;Lo DC;Baldwin AS
多形性胶质母细胞瘤（GBM）预后不良，仍然缺乏有效的治疗。胶质母细胞瘤干细胞（GSC）驱动肿瘤形成，侵袭和耐药性，因此，是确定疾病控制新疗法的研究重点。在此，我们确定IKK和NF-κB信号通路参与GSC的维持。如在肿瘤球形成中分析的，抑制该途径损害自我更新，如在脑切片培养中分析的，损害GBM扩增。有趣的是，NF-κB通路的经典分支和非经典分支都显示出对这种表型有贡献。GBM中NF-κB活化的一个来源涉及TGF-β/TAK 1信号传导轴。总之，我们的研究结果证明了NF-κB通路在GSC中的作用，并为其作为胶质母细胞瘤治疗靶点的潜力提供了机制基础。
Glioblastoma multiforme (GBM) carries a poor prognosis and continues to lack effective treatments. Glioblastoma stem cells (GSCs) drive tumor formation, invasion, and drug resistance and, as such, are the focus of studies to identify new therapies for disease control. Here, we identify the involvement of IKK and NF-κB signaling in the maintenance of GSCs. Inhibition of this pathway impairs self-renewal as analyzed in tumorsphere formation and GBM expansion as analyzed in brain slice culture. Interestingly, both the canonical and non-canonical branches of the NF-κB pathway are shown to contribute to this phenotype. One source of NF-κB activation in GBM involves the TGF-β/TAK1 signaling axis. Together, our results demonstrate a role for the NF-κB pathway in GSCs and provide a mechanistic basis for its potential as a therapeutic target in glioblastoma.