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Accession IconGSE49161

A Proneural to Mesenchymal Transition Mediated by NFkB Promotes Radiation Resistance in Glioblastoma (part 1)

Organism Icon Homo sapiens
Sample Icon 15 Downloadable Samples
Technology Badge Icon Affymetrix Human Genome U133A 2.0 Array (hgu133a2)

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SUMMARY Despite numerous genome-wide association studies involving glioblastoma (GBM), few therapeutic targets have been identified for this disease. Using patient derived glioma sphere cultures (GSCs), we have found that a subset of the proneural (PN) GSCs undergo transition to a mesenchymal (MES) state in a TNFa/NFkB dependent manner with an associated enrichment of CD44 sub-populations and radio-resistant phenotypes. To the contrary, MES GSCs exhibit constitutive NFkB activation, CD44 enrichment and radio-resistance. Patients whose tumors exhibit a higher MES metagene, increased expression of CD44, or activated NFkB were associated with poor radiation response and shorter survival. Our results indicate that NFkB activation mediated MES differentiation and radiation resistance presents an attractive therapeutic target for GBM.
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