|
| Status |
Public on Jun 30, 2014 |
| Title |
Insights into the invasiveness of triple negative breast cancer from genome-wide profiling of transcription factor AP-1 (ChIP-seq) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Triple negative breast cancer (TNBC) is an aggressive clinical phenotype, and accounts for 15% to 20% of all breast cancers. The molecular determinants of malignant cell behaviors in TNBC remain largely unknown. We find that the AP-1 transcription factor component, Fra-1, is overexpressed in basal-like breast tumors, and its expression level has high prognostic significance. Depletion of Fra-1 or its heterodimeric partner c-Jun inhibits the proliferative and invasive phenotypes in TNBC cells. To gain insights into the transcriptional regulatory networks of AP-1 in TNBC cells, we combine genome-wide ChIP-seq with loss-of-function transcriptome analyses. We observe dysregulation of direct targets of the Fra-1/c-Jun heterodimer involved in cell proliferation, cell adhesion, and cell-cell contact. Intriguingly, we find that AP-1 mediates downregulation of E-cadherin through direct transcriptional induction of ZEB2. This work sheds light on the mechanisms and pathways by which TNBC acquires invasiveness and proliferative propensity.
|
| |
|
| Overall design |
Examination of genome-wide binding sites of AP-1 transcription factor components, Fra-1 and c-Jun, in BT549 breast cancer cell line.
|
| |
|
| Contributor(s) |
Qiao Y, Dahlman-Wright K, Jonsson P, Williams C, Xu L, Sinha I, Zhao C |
| Citation(s) |
24830720 |
| Submission date |
Apr 17, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Chunyan Zhao |
| E-mail(s) |
chunyan.zhao@ki.se
|
| Phone |
46-8-52481126
|
| Fax |
46-8-7745538
|
| Organization name |
Karolinska Institute
|
| Department |
Biosciences and Nutrition
|
| Street address |
Hälsovägen 7-9
|
| City |
Stockholm |
| ZIP/Postal code |
SE-171 77 |
| Country |
Sweden |
| |
|
| Platforms (1) |
| GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
|
| Samples (4)
|
|
| This SubSeries is part of SuperSeries: |
| GSE46441 |
Insights into the invasiveness of triple negative breast cancer from genome-wide profiling of transcription factor AP-1 |
|
| Relations |
| BioProject |
PRJNA197435 |
| SRA |
SRP021169 |
Less...
More...