IKK/NF-κB signaling contributes to glioblastoma stem cell maintenance
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 involveme...
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| Veröffentlicht in: | Oncotarget 2016-10, Vol.7 (43), p.69173-69187 |
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| creator | Rinkenbaugh, Amanda L Cogswell, Patricia C Calamini, Barbara Dunn, Denise E Persson, Anders I Weiss, William A Lo, Donald C Baldwin, Albert S |
| description | 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. |
| doi_str_mv | 10.18632/oncotarget.12507 |
| format | Article |
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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. 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| source | Freely Accessible Journals; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; PubMed Central |
| subjects | 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 Neoplastic Stem Cells - metabolism NF-kappa B - genetics NF-kappa B - metabolism Priority Research Paper Rats RNA Interference Signal Transduction Spheroids, Cellular - metabolism Tissue Culture Techniques Transforming Growth Factor beta - metabolism |
| title | IKK/NF-κB signaling contributes to glioblastoma stem cell maintenance |
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