IKK/NF-κB signaling contributes to glioblastoma stem cell maintenance

Oncotarget. 2016 Oct 25;7(43):69173-69187. doi: 10.18632/oncotarget.12507.


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.

Keywords: NF-κB; cancer stem cells; glioblastoma; tumor-initiating cells.

MeSH terms

  • Animals
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Self Renewal*
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism*
  • MAP Kinase Kinase Kinases / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Neoplastic Stem Cells / metabolism*
  • RNA Interference
  • Rats
  • Signal Transduction*
  • Spheroids, Cellular / metabolism
  • Tissue Culture Techniques
  • Transforming Growth Factor beta / metabolism


  • NF-kappa B
  • Transforming Growth Factor beta
  • I-kappa B Kinase
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7