Exploring the roles of Notch inhibitors and STAT3 inhibitors in the regulation of liver cancer proliferation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1079306 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28053532_1.fastq.gz | Fastqsanger.gz | |||
| SRR28053532_2.fastq.gz | Fastqsanger.gz | |||
| SRR28053533_1.fastq.gz | Fastqsanger.gz | |||
| SRR28053533_2.fastq.gz | Fastqsanger.gz | |||
| SRR28053534_1.fastq.gz | Fastqsanger.gz |
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Project description: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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