|
| Status |
Public on Jul 31, 2017 |
| Title |
Enhancer reprogramming promotes pancreatic cancer progression and metastasis [ATAC-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies, owing in part to its propensity for metastasis. Here, we used an organoid culture system to investigate how transcription and the enhancer landscape become altered during each stage of PDA progression. This approach revealed that the metastatic transition is accompanied by massive, and recurrent alterations in enhancer activity. We implicate the transcription factors FOXA1 and GATA5 as drivers of enhancer activation in this system, a mechanism that we show renders PDA cells more invasive and less anchorage-dependent for growth in vitro, as well as more metastatic in vivo. FOXA1 and GATA5 were found to activate a foregut endoderm transcriptional program in PDA cells, without altering genes associated with the epithelial-to- mesenchymal transition. Collectively, our study implicates FOXA1/GATA5 upregulation, enhancer reprogramming, and a novel retrograde developmental transition in PDA progression and metastasis.
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| |
|
| Overall design |
ATAC-Seq of mouse PDA organoids
|
| |
|
| Contributor(s) |
Roe J, Vakoc CR |
| Citation(s) |
28757253 |
| |
| Submission date |
May 24, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Jae Seok Roe |
| E-mail(s) |
jroe@yonsei.ac.kr
|
| Organization name |
Yonsei University
|
| Street address |
Yonsei-ro, 50
|
| City |
Seoul |
| ZIP/Postal code |
03722 |
| Country |
South Korea |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE99311 |
Enhancer reprogramming promotes pancreatic cancer progression and metastasis |
|
| Relations |
| BioProject |
PRJNA387924 |
| SRA |
SRP107980 |
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