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| Status |
Public on Jun 19, 2013 |
| Title |
Crosstalk between the STAT3, NF-kB and Notch signaling pathways in glioblastoma stem cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
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.
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| Contributor(s) |
Garner JM, Fan M, Zang CH, Du Z, Sims M, Davidoff AM, Pfeffer LM |
| Citation(s) |
23902772 |
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| Submission date |
Jun 18, 2013 |
| Last update date |
Aug 16, 2018 |
| Contact name |
Jo Meagan Garner |
| Organization name |
University of Tennessee Health Science Center
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| Department |
Pathology
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| Lab |
Pfeffer
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| Street address |
19 S. Manassas St.
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| City |
Memphis |
| State/province |
United States |
| ZIP/Postal code |
38103 |
| Country |
USA |
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| Platforms (1) |
| GPL6947 |
Illumina HumanHT-12 V3.0 expression beadchip |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA208872 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE48079_RAW.tar |
6.2 Mb |
(http)(custom) |
TAR |
| GSE48079_non_normalized.txt.gz |
2.0 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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