|
| Status |
Public on Jan 20, 2016 |
| Title |
Genome-wide profiling of inflammatory cistrome reveals AP-1/c-Jun as a key regulator of TNFalpha-mediated triple-negative breast cancer progression [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Triple-negative breast cancer (TNBC) represents a highly aggressive form of breast cancer with limited treatment options. Proinflammatory cytokines such as TNF can facilitate tumor progression and metastasis. However, our knowledge of the molecular mechanisms underlying TNBC progression mediated by inflammation is still limited. Here, we define the AP-1 transcription factor c-Jun cistrome, which is comprised of 13800 binding sites responsive to TNFalpha-induced signaling in TNBC cells. In addition, we show that c-Jun regulates nearly a third of the TNFalpha-elicited transcriptome. Expression of the c-Jun-regulated pro-invasion gene program is strongly associated with clinical outcomes in TNBCs. Mechanistically; we demonstrate that c-Jun drives TNFalpha-mediated TNBC tumorigenicity by transcriptional regulation of Ninj1. As exemplified by the c-Jun bound CXC chemokine genes clustered on chromosome 4, we demonstrate that NF-kB might be a pioneer factor and is required for the regulation of TNFalpha-inducible inflammatory genes, whereas c-Jun has little effect. Together, our results uncover AP-1 as an important determinant for inflammation-induced cancer progression, rather than inflammatory response.
|
| |
|
| Overall design |
BT549 cells were serum-starved overnight and then treated with or without TNFalpha for 3 hours.
|
| |
|
| Contributor(s) |
Qiao Y, Dahlman-Wright K, Jonsson P, Zhao C, Sinha I |
| Citation(s) |
26792858 |
| Submission date |
Aug 12, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Karin Dahlman-Wright |
| Organization name |
Karolinska Institutet
|
| Department |
Department of Biosciences and Nutrition
|
| Lab |
Medicinaren 25/Neo
|
| Street address |
Blickagången 16
|
| City |
Huddinge |
| ZIP/Postal code |
14157 |
| Country |
Sweden |
| |
|
| Platforms (1) |
| GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
|
| Samples (4)
|
|
| This SubSeries is part of SuperSeries: |
| GSE71977 |
Genome-wide profiling of inflammatory cistrome reveals AP-1/c-Jun as a key regulator of TNFalpha-mediated triple-negative breast cancer progression. |
|
| Relations |
| BioProject |
PRJNA292652 |
| SRA |
SRP062313 |
Less...
More...