E-GEOD-48079 - Crosstalk between the STAT3, NF-kB and Notch signaling pathways in glioblastoma stem cells

Released on 19 June 2013, last updated on 3 June 2014
Homo sapiens
Samples (6)
Array (1)
Protocols (6)
In this study, we describe a novel relationship between glioblastoma CSCs and the Notch pathway, which involves the constitutive activation of STAT3 and NF-κB signaling. We demonstrate that adherent glioma CSCs exhibit characteristics previously described for CSCs grown in suspension culture. The expression of CD133, Sox2 and Nestin increased when compared to glioma cells grown in monolayer, and the adherent CSCs were ~100 times more tumorigenic in vivo than monolayer cultured glioma cells. We also found that while the STAT3 and NF-κB signaling pathways are constitutively activated in glioma lines, these pathways are dramatically activated in glioma CSCs. Treatment with STAT3 inhibitors led to a loss of nuclear activation of STAT3 signaling and suppression of growth in both monolayer and CSC conditions. There was a markedly greater growth suppressive effect on glioma CSCs, suggesting that targeted therapy of these key pathways in glioma CSCs may be possible. To further investigate potential biomarkers in glioma CSCs, microarray analysis was performed and revealed deregulation of the Notch signaling pathway. This constitutive activation of STAT3, NF-κB, and Notch pathways in glioma CSCs helps identify novel therapeutic targets for the treatment of glioma. GBM6 cells were continuously maintained as subcutaneous xenografts in NSG mice, and monolayer and CSC cultures were derived from freshly harvested tumor tissue. A total of 6 samples were subjected to microarray analysis, with three biological replicates for each experimental condition.
Experiment type
transcription profiling by array 
Jo Meagan Garner <geo@ncbi.nlm.nih.gov>, Andrew M Davidoff, Chuan H Zang, Jo M Garner, Lawrence M Pfeffer, Meiyun Fan, Michelle Sims, Ziyan Du
Investigation descriptionE-GEOD-48079.idf.txt
Sample and data relationshipE-GEOD-48079.sdrf.txt
Processed data (1)E-GEOD-48079.processed.1.zip
Array designA-MEXP-1171.adf.txt