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| Status |
Public on Jul 08, 2015 |
| Title |
EAG2 potassium channel with evolutionarily conserved function as a brain tumor target |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Characterizing the impact of pharmacological and shRNA-mediated silencing of EAG2 in medulloblastoma.
Medulloblastoma (MB) is the most common pediatric CNS malignancy. Previously, we demonstrated that overexpression of the ion channel EAG2, identified in a subset of histological and molecular subtypes of this disease, functionally contributes to tumor progression (PMID: 22855790). Here, we demonstrate the evolutionarily conserved function of EAG2 potassium channel in promoting brain tumor growth and metastasis, delineate downstream pathways and uncover a co-option mechanism for different potassium channels to regulate mitotic cell volume and tumor progression. We show that EAG2 potassium channel is enriched at the trailing edge of migrating MB cells to regulate local cell volume dynamics, thereby facilitating cell motility. We identify the FDA- approved antipsychotic drug thioridazine as an EAG2 channel blocker that reduces xenografted MB growth and metastasis, and present a case report of repurposing thioridazine for treating a human patient. Our findings thus illustrate the potential of targeting ion channels in cancer treatment.
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| Overall design |
The goal of this analysis was to determine the transcriptional consequences of pharmacological (i.e. astemizole) or shRNA-mediated inhibition/suppression of EAG2 in low passage medulloblastoma cell lines. This analysis was performed in an effort to characterize evolutionarily conserved role of EAG2 in mediating tumor growth and metastasis. Pathway analysis was subsequently performed and compared to results obtained in a Drosophila model.
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| Contributor(s) |
Huang X, Dubuc A |
| Citation(s) |
26258683 |
| Submission date |
Jul 07, 2015 |
| Last update date |
Mar 15, 2019 |
| Contact name |
Adrian Dubuc |
| E-mail(s) |
adubuc@bwh.harvard.edu
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| Organization name |
Brigham and Women's Hospital
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| Street address |
75 Francis St, 5-5066 Shapiro Building
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| City |
Boston |
| State/province |
Massachussetts |
| ZIP/Postal code |
01760 |
| Country |
USA |
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| Platforms (1) |
| GPL16686 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA289065 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE70576_RAW.tar |
104.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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