Title |
Genome-wide Profiling of AP-1–Regulated Transcription Provides Insights into the Invasiveness of Triple-Negative Breast Cancer
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Published in |
Cancer Research, July 2014
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DOI | 10.1158/0008-5472.can-13-3396 |
Pubmed ID | |
Authors |
Chunyan Zhao, Yichun Qiao, Philip Jonsson, Jian Wang, Li Xu, Pegah Rouhi, Indranil Sinha, Yihai Cao, Cecilia Williams, Karin Dahlman-Wright |
Abstract |
Triple-negative breast cancer (TNBC) is an aggressive clinical subtype accounting for up to 20% of all breast cancers, but its malignant determinants remain largely undefined. Here, we show that in TNBC the overexpression of Fra-1, a component of the transcription factor AP-1, offers prognostic potential. Fra-1 depletion or its heterodimeric partner c-Jun inhibits the proliferative and invasive phenotypes of TNBC cells in vitro. Similarly, RNAi-mediated attenuation of Fra-1 or c-Jun reduced cellular invasion in vivo in a zebrafish tumor xenograft model. Exploring the AP-1 cistrome and the AP-1-regulated transcriptome, we obtained insights into the transcriptional regulatory networks of AP-1 in TNBC cells. Among the direct targets identified for Fra-1/c-Jun involved in proliferation, adhesion, and cell-cell contact, we found that AP-1 repressed the expression of E-cadherin by transcriptional upregulation of ZEB2 to stimulate cell invasion. Overall, this work illuminates the pathways through which TNBC cells acquire invasive and proliferative properties. Cancer Res; 74(14); 3983-94. ©2014 AACR. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 33% |
Unknown | 2 | 67% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 120 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 31 | 26% |
Researcher | 26 | 22% |
Student > Bachelor | 11 | 9% |
Student > Master | 10 | 8% |
Student > Doctoral Student | 6 | 5% |
Other | 13 | 11% |
Unknown | 23 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 37 | 31% |
Biochemistry, Genetics and Molecular Biology | 36 | 30% |
Medicine and Dentistry | 11 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 3% |
Immunology and Microbiology | 2 | 2% |
Other | 5 | 4% |
Unknown | 26 | 22% |