title: IKK/NF-κB signaling contributes to glioblastoma stem cell maintenance.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA.|Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Rinkenbaugh
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.|Chordoma Foundation, Durham, NC, USA.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Cogswell
authors.affiliation: Center for Drug Discovery and Department of Neurobiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Calamini
authors.affiliation: Center for Drug Discovery and Department of Neurobiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Denise E
authors.initials: DE
authors.lastname: Dunn
authors.affiliation: Helen Diller Family Comprehensive Cancer Center and Department of Neurology, University of California, San Francisco, CA, USA.|Department of Neurological Surgery and Brain Tumor Research Center, University of California, San Francisco, CA, USA.
authors.forename: Anders I
authors.initials: AI
authors.lastname: Persson
authors.affiliation: Helen Diller Family Comprehensive Cancer Center and Department of Neurology, University of California, San Francisco, CA, USA.|Department of Neurological Surgery and Brain Tumor Research Center, University of California, San Francisco, CA, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Weiss
authors.affiliation: Center for Drug Discovery and Department of Neurobiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Donald C
authors.initials: DC
authors.lastname: Lo
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Albert S
authors.initials: AS
authors.lastname: Baldwin
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D000066673:Cell Self Renewal; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D015398:Signal Transduction; D018874:Spheroids, Cellular / Q000378:metabolism; D046509:Tissue Culture Techniques; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D051550:I-kappa B Kinase; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D016212:Transforming Growth Factor beta; D000099151:MAP Kinase Kinase Kinase 7
keywords: NF-κB; cancer stem cells; glioblastoma; tumor-initiating cells