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| Status |
Public on Nov 08, 2016 |
| Title |
FOXK2 ChIP sequencing in non-treated MCF-7 cells |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Although clinically associated with severe intellectual disability, West syndrome, Dandy-Walker malformation, and syndactyly, the biological function of FOXK2 remains poorly explored. Here we report that FOXK2 acts as a transcription repressor. Strikingly, FOXK2 interacts with multiple transcription corepressor complexes including NCoR/SMRT, SIN3A, NuRD, and REST/CoREST. FOXK2 assembles these transcription programs to repress a cohort of genes including HIF1 and EZH2 and to regulate several signaling pathways including the hypoxic response that is critically implicated in tumor development and progression. We showed that FOXK2 inhibits the proliferation and invasion of breast cancer cells in vitro and suppresses the growth and metastasis of breast cancer in vivo. Interestingly, FOXK2 is transactivated by ERand transrepressed via reciprocal successive feedback by HIF1/EZH2. Significantly, the expression of FOXK2 is progressively lost during breast cancer progression, leading to elevated expression of EZH2, an eminent feature of aggressive breast cancer. Indeed, the expression of FOXK2 is inversely correlated with that of EZH2 and HIF1in breast carcinomas, and low FOXK2 expression is strongly correlated with higher histologic grades, positive lymph nodes, and ER/PR/Her2 status, all indicators of poor prognosis. Our experiments revealed that FOXK2 is massively involved in transcription repression, providing a molecular basis for the understanding of the mechanistic action of FOXK2. Our study identified the ER-FOXK2-HIF1/EZH2 axis in breast cancer progression, supporting the pursuit of these molecules as therapeutic targets for breast cancer intervention.
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| Overall design |
Examination of FOXK2 target genes in MCF-7 cells
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| Contributor(s) |
Shan L, Zhou X |
| Citation(s) |
27773593 |
| BioProject |
PRJNA327721 |
| Submission date |
Jul 11, 2016 |
| Last update date |
Jun 22, 2019 |
| Contact name |
Xinhua Liu |
| E-mail(s) |
liuxinhua@tmu.edu.cn
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| Organization name |
Hangzhou Normal University
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| Department |
School of Basic Medicine
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| Street address |
NO.2318, Yuhangtang road
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| City |
Hangzhou |
| State/province |
Zhejiang |
| ZIP/Postal code |
311121 |
| Country |
China |
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| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL23525 |
Complete Genomics (Homo sapiens) |
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| Samples (4)
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| Relations |
| SRA |
SRP077859 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE84241_RAW.tar |
627.3 Mb |
(http)(custom) |
TAR (of BED, BW) |
SRA Run Selector |
| Processed data provided as supplementary file |
| Raw data are available in SRA |
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