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| Status |
Public on Dec 31, 2015 |
| Title |
Drug specific epigenetic reprogramming leads to increased cellular invasion in ERα positive breast cancer via de novo cholesterol biosynthesis. |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Endocrine therapy resistance remains a critical problem in the treatment of estrogen receptor alpha (ERα) breast cancer. Endocrine therapies target ERα via different modes of action. Drug resistance involves drug specific remodeling of the transcriptional and regulatory landscape. Using epigenomics and transcriptomics, we demonstrate that resistance to aromatase inhibitors (AI) induces phenotypical changes through epigenetic activation of cholesterol biosynthesis (CB) and keratin 80. Epigenetic activation is stable and involves both large topological domains and punctuated activation of single enhancers and super-enhancers. Specialized cancer cells expressing high levels of keratin 80 lead invasion through the extracellular matrix. Strikingly, we demonstrate that anti-cholesterol strategies can effectively arrest breast cancer invasion. Our work identifies a robust strategy to target resistant invasive breast cancer.
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| Overall design |
All cell lines were grown in their respective media until they reached 70% confluency. Specifically, MCF7 were grown in DMEM+10% FBS and 1% Pen-Sprep-Glutamine. MCF7T as MCF7 with the addition of 100nM Tamoxifen. MCF7F as MCF7 with the addition of 100nM Fulvestrant. LTED were grown in DMEM without phenol + 10% DCS-FBS and1% Pen-Sprep-Glutamine. LTEDT as LTED with the addition of 100nM Tamoxifen. LTEDF as LTED with the addition of 100nM of Fulvestrant. All chemicals are purchased from Sigma. ChIP-seq was performed using Illumina methodology.
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| Contributor(s) |
Magnani L |
| Citation(s) |
26610607 |
| Submission date |
Aug 19, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Luca Magnani |
| E-mail(s) |
magnanirimini78@gmail.com
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| Organization name |
Imperial College London
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| Department |
Surgery and Cancer
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| Lab |
Magnani's Lab
|
| Street address |
DuCane road
|
| City |
London |
| ZIP/Postal code |
W120NN |
| Country |
United Kingdom |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA259193 |
| SRA |
SRP045706 |
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