PUBLICATION
Genome-wide Profiling of AP-1–Regulated Transcription Provides Insights into the Invasiveness of Triple-Negative Breast Cancer
- Authors
- Zhao, C., Qiao, Y., Jonsson, P., Wang, J., Xu, L., Rouhi, P., Sinha, I., Cao, Y., Williams, C., Dahlman-Wright, K.
- ID
- ZDB-PUB-140517-9
- Date
- 2014
- Source
- Cancer research 74(14): 3983-94 (Journal)
- Registered Authors
- Sinha, Indranil
- Keywords
- none
- MeSH Terms
-
- Cadherins/metabolism
- Cell Line, Tumor
- Cell Proliferation
- Female
- Gene Expression Profiling*
- Gene Expression Regulation, Neoplastic*
- Gene Knockdown Techniques
- Homeodomain Proteins/metabolism
- Humans
- MAP Kinase Signaling System
- Models, Biological
- Neoplasm Invasiveness
- Neoplasms, Basal Cell
- Phosphatidylinositol 3-Kinases/metabolism
- Prognosis
- Proto-Oncogene Proteins c-akt/metabolism
- Proto-Oncogene Proteins c-fos/genetics
- Proto-Oncogene Proteins c-fos/metabolism
- Proto-Oncogene Proteins c-jun/genetics
- Proto-Oncogene Proteins c-jun/metabolism
- Repressor Proteins/metabolism
- Transcription Factor AP-1/genetics
- Transcription Factor AP-1/metabolism*
- Transcription, Genetic*
- Transcriptome
- Triple Negative Breast Neoplasms/genetics*
- Triple Negative Breast Neoplasms/metabolism*
- Triple Negative Breast Neoplasms/mortality
- Triple Negative Breast Neoplasms/pathology
- PubMed
- 24830720 Full text @ Cancer Res.
Citation
Zhao, C., Qiao, Y., Jonsson, P., Wang, J., Xu, L., Rouhi, P., Sinha, I., Cao, Y., Williams, C., Dahlman-Wright, K. (2014) Genome-wide Profiling of AP-1–Regulated Transcription Provides Insights into the Invasiveness of Triple-Negative Breast Cancer. Cancer research. 74(14):3983-94.
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 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping