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| Status |
Public on Feb 02, 2016 |
| Title |
The PGC-1α/ERRα Axis Represses One-Carbon Metabolism and Promotes Sensitivity to Anti-Folate Therapy in Breast Cancer [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Reprogramming of cellular metabolism plays a central role in fuelling malignant transformation, and AMPK as well as the PGC-1α/ERRα axis are key regulators of this process. Intersection of gene expression and binding event datasets in breast cancer cells shows that activation of AMPK significantly increases the expression of PGC-1α/ERRα and promotes the binding of ERRα to its cognate sites. Unexpectedly, the data also reveal that ERRα, in concert with PGC-1α, negatively regulates the expression of several one-carbon metabolism genes resulting in substantial perturbations in purine biosynthesis. This PGC-1α/ERRα-mediated repression of one-carbon metabolism promotes the sensitivity of breast cancer cells and tumors to the anti-folate drug methotrexate. These data implicate the PGC-1α/ERRα axis as a core regulatory node of folate cycle metabolism and further suggest that activators of AMPK could be used to modulate this pathway in cancer.
We used microarrays to detail the global programme of gene expression following AMPK activation by AICAR in BT474 breast cancer cells.
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| Overall design |
BT474 breast cancer cells were treated for 24h with vehicle or the AMPK activator AICAR and RNA was then purified for microarray analysis. Experiments were performed in duplicate for each condition.
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| Contributor(s) |
Audet-Walsh E, Papadopoli D |
| Citation(s) |
26804918 |
| Submission date |
Dec 10, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Etienne Audet-Walsh |
| E-mail(s) |
etienne.audet-walsh@crchudequebec.ulaval.ca
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| Organization name |
Université Laval
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| Department |
Molecular Medicine
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| Street address |
2705 boulevard Laurier
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| City |
Québec City |
| State/province |
QC |
| ZIP/Postal code |
G1V 4G2 |
| Country |
Canada |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE75877 |
The PGC-1α/ERRα Axis Represses One-Carbon Metabolism and Promotes Sensitivity to Anti-Folate Therapy in Breast Cancer |
|
| Relations |
| BioProject |
PRJNA305586 |
| SRA |
SRP067217 |
