2. Academic Validation
  3. IKK/NF-κB signaling contributes to glioblastoma stem cell maintenance

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

  • Oncotarget. 2016 Oct 25;7(43):69173-69187. doi: 10.18632/oncotarget.12507.
Amanda L Rinkenbaugh 1 2,  Patricia C Cogswell 2 3,  Barbara Calamini 4,  Denise E Dunn 4,  Anders I Persson 5 6,  William A Weiss 5 6,  Donald C Lo 4,  Albert S Baldwin 2
Affiliations

Affiliations

  • 1 Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA.
  • 2 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
  • 3 Chordoma Foundation, Durham, NC, USA.
  • 4 Center for Drug Discovery and Department of Neurobiology, Duke University Medical Center, Durham, NC, USA.
  • 5 Helen Diller Family Comprehensive Cancer Center and Department of Neurology, University of California, San Francisco, CA, USA.
  • 6 Department of Neurological Surgery and Brain Tumor Research Center, University of California, San Francisco, CA, USA.
PMID: 27732951 DOI: 10.18632/oncotarget.12507
Abstract

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.

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