| Title |
Enhancer Reprogramming Promotes Pancreatic Cancer Metastasis
|
|---|---|
| Published in |
Cell, July 2017
|
| DOI | 10.1016/j.cell.2017.07.007 |
| Pubmed ID | |
| Authors |
Jae-Seok Roe, Chang-Il Hwang, Tim D.D. Somerville, Joseph P. Milazzo, Eun Jung Lee, Brandon Da Silva, Laura Maiorino, Hervé Tiriac, C. Megan Young, Koji Miyabayashi, Dea Filippini, Brianna Creighton, Richard A. Burkhart, Jonathan M. Buscaglia, Edward J. Kim, Jean L. Grem, Audrey J. Lazenby, James A. Grunkemeyer, Michael A. Hollingsworth, Paul M. Grandgenett, Mikala Egeblad, Youngkyu Park, David A. Tuveson, Christopher R. Vakoc |
| Abstract |
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 discrete stages of disease progression in a PDA mouse model. This approach revealed that the metastatic transition is accompanied by massive and recurrent alterations in enhancer activity. We implicate the pioneer factor FOXA1 as a driver of enhancer activation in this system, a mechanism that renders PDA cells more invasive and less anchorage-dependent for growth in vitro, as well as more metastatic in vivo. In this context, FOXA1-dependent enhancer reprogramming activates a transcriptional program of embryonic foregut endoderm. Collectively, our study implicates enhancer reprogramming, FOXA1 upregulation, and a retrograde developmental transition in PDA metastasis. |
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X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 32 | 39% |
| United Kingdom | 6 | 7% |
| Netherlands | 2 | 2% |
| France | 2 | 2% |
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| India | 2 | 2% |
| Sweden | 1 | 1% |
| Israel | 1 | 1% |
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| Other | 9 | 11% |
| Unknown | 25 | 30% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
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| Scientists | 36 | 43% |
| Practitioners (doctors, other healthcare professionals) | 4 | 5% |
| Science communicators (journalists, bloggers, editors) | 3 | 4% |
Mendeley demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 609 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 152 | 25% |
| Researcher | 89 | 15% |
| Student > Master | 52 | 9% |
| Student > Bachelor | 51 | 8% |
| Student > Doctoral Student | 32 | 5% |
| Other | 82 | 13% |
| Unknown | 151 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 224 | 37% |
| Agricultural and Biological Sciences | 111 | 18% |
| Medicine and Dentistry | 54 | 9% |
| Immunology and Microbiology | 18 | 3% |
| Engineering | 10 | 2% |
| Other | 35 | 6% |
| Unknown | 157 | 26% |