|
| Status |
Public on Jul 17, 2020 |
| Title |
IL6/STAT3 co-opts ER/FOXA1 regulatory elements to drive metastasis in breast cancer (ChIP-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Interleukin 6 (IL6) signaling has been associated with an aggressive and metastatic phenotype in multiple solid tumors including breast cancer, but its mechanism of action in mediating tumor progression and treatment response is not clear. By exploiting a clinically relevant intraductal xenograft model of estrogen receptor positive (ER+) breast cancer, we demonstrate that IL6 increases both primary tumor growth and distant metastases. By integrating pre-clinical models and clinical specimens, we show that signal transducer and activator of transcription 3 (STAT3) mediates IL6-induced activation of a metastatic gene program from enhancer-elements shared with ER and its pioneer factor FOXA1. Although IL6 activated STAT3 and ER/FOXA1 share cis-regulatory regions, STAT3 drives transcription independent of ER and FOXA1 function, and the IL6/STAT3 gene program is not influenced by ER-targeted therapies, decoupling these two important pathways. This demonstrates that ER/FOXA1 and IL6/STAT3 are two parallel, but independent actionable pathways controlling breast cancer progression.
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| |
|
| Overall design |
ChIP-seq in breast cancer cell lines in response to IL6 and in clinical samples.
ChIP-sequencing on ER on T47D cells with FOXA1 siRNA with or without IL6
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| |
|
| Contributor(s) |
Siersbaek R, Chernukin I, Carroll JS |
| Citation(s) |
32679107 |
| Submission date |
Feb 01, 2019 |
| Last update date |
Aug 01, 2020 |
| Contact name |
Jason Carroll |
| E-mail(s) |
Jason.Carroll@cruk.cam.ac.uk
|
| Phone |
+44 1223 769649
|
| Organization name |
Cancer Research UK, Cambridge Institute
|
| Street address |
Li Ka Shing Centre, Robinson Way
|
| City |
Cambridge |
| ZIP/Postal code |
CB2 ORE |
| Country |
United Kingdom |
| |
|
| Platforms (2) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (143)
|
|
| This SubSeries is part of SuperSeries: |
| GSE126006 |
IL6/STAT3 co-opts ER/FOXA1 regulatory elements to drive metastasis in breast cancer |
|
| Relations |
| BioProject |
PRJNA518885 |
| SRA |
SRP183163 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE126004_jc5554_3840_pstat3-X-jc5554_3840_pstat3_input_peaks.narrowPeak.gz |
41.5 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_jc5555_3487_pstat3-X-jc5555_3487_pstat3_input_peaks.narrowPeak.gz |
356.6 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_jc5572_3840_er-X-jc5572_3840_er_input_peaks.narrowPeak.gz |
139.7 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_jc5573_3487_er-X-jc5573_3487_er_input_peaks.narrowPeak.gz |
459.2 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_jc5583_3487_foxa1-X-jc5583_3487_foxa1_input_peaks.narrowPeak.gz |
296.7 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_mcf7_er_il6-X-mcf7_er_il6_input_peaks.narrowPeak.gz |
1.8 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_mcf7_er_pbs-X-mcf7_er_pbs_input_peaks.narrowPeak.gz |
2.2 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_mcf7_foxa1_il6-X-mcf7_foxa1_il6_input_peaks.narrowPeak.gz |
1.8 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_mcf7_foxa1_veh-X-mcf7_foxa1_veh_input_peaks.narrowPeak.gz |
1.8 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_mcf7_h3k27ac_il6-X-mcf7_h3k27ac_il6_input_peaks.broadPeak.gz |
1.8 Mb |
(ftp)(http) |
BROADPEAK |
| GSE126004_mcf7_h3k27ac_veh-X-mcf7_h3k27ac_veh_input_peaks.broadPeak.gz |
1.9 Mb |
(ftp)(http) |
BROADPEAK |
| GSE126004_mcf7_pstat3_il6-X-mcf7_pstat3_il6_input_peaks.narrowPeak.gz |
1.6 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_mcf7_pstat3_pbs-X-mcf7_pstat3_pbs_input_peaks.narrowPeak.gz |
27.0 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_mcf7_stat3_il6-X-mcf7_stat3_il6_input_peaks.narrowPeak.gz |
1.0 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_mcf7_stat3_pbs-X-mcf7_stat3_pbs_input_peaks.narrowPeak.gz |
370.3 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_sicont_il6-X-sicont_il6_input_peaks.narrowPeak.gz |
1.2 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_sicont_veh-X-sicont_veh_input_peaks.narrowPeak.gz |
601.0 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_sifoxa1_il6-X-sifoxa1_il6_input_peaks.narrowPeak.gz |
755.5 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_sifoxa1_veh-X-sifoxa1_veh_input_peaks.narrowPeak.gz |
559.7 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_t47d_er_il6-X-t47d_er_il6_input_peaks.narrowPeak.gz |
405.3 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_t47d_er_veh-X-t47d_er_veh_input_peaks.narrowPeak.gz |
404.4 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_t47d_foxa1_il6-X-t47d_foxa1_il6_input_peaks.narrowPeak.gz |
2.5 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_t47d_foxa1_veh-X-t47d_foxa1_veh_input_peaks.narrowPeak.gz |
1.6 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_t47d_h3k27ac_il6-X-t47d_h3k27ac_il6_input_peaks.broadPeak.gz |
1.9 Mb |
(ftp)(http) |
BROADPEAK |
| GSE126004_t47d_h3k27ac_sictl_il6-X-t47d_h3k27ac_sictl_il6_input_peaks.broadPeak.gz |
2.1 Mb |
(ftp)(http) |
BROADPEAK |
| GSE126004_t47d_h3k27ac_sictl_pbs-X-t47d_h3k27ac_sictl_pbs_input_peaks.broadPeak.gz |
2.2 Mb |
(ftp)(http) |
BROADPEAK |
| GSE126004_t47d_h3k27ac_sifoxa1_il6-X-t47d_h3k27ac_sifoxa1_il6_input_peaks.broadPeak.gz |
2.1 Mb |
(ftp)(http) |
BROADPEAK |
| GSE126004_t47d_h3k27ac_sifoxa1_pbs-X-t47d_h3k27ac_sifoxa1_pbs_input_peaks.broadPeak.gz |
2.1 Mb |
(ftp)(http) |
BROADPEAK |
| GSE126004_t47d_h3k27ac_veh-X-t47d_h3k27ac_veh_input_peaks.broadPeak.gz |
1.9 Mb |
(ftp)(http) |
BROADPEAK |
| GSE126004_t47d_pstat3_il6-X-t47d_pstat3_il6_input_peaks.narrowPeak.gz |
1.5 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_t47d_pstat3_sictl_il6-X-t47d_pstat3_sictl_il6_input_peaks.narrowPeak.gz |
2.9 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_t47d_pstat3_sictl_pbs-X-t47d_pstat3_sictl_pbs_input_peaks.narrowPeak.gz |
3.3 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_t47d_pstat3_sifoxa1_il6-X-t47d_pstat3_sifoxa1_il6_input_peaks.narrowPeak.gz |
2.9 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_t47d_pstat3_sifoxa1_pbs-X-t47d_pstat3_sifoxa1_pbs_input_peaks.narrowPeak.gz |
9.8 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_t47d_pstat3_veh-X-t47d_pstat3_veh_input_peaks.narrowPeak.gz |
409 b |
(ftp)(http) |
NARROWPEAK |
| GSE126004_t47d_stat3_il6-X-t47d_stat3_il6_input_peaks.narrowPeak.gz |
853.7 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE126004_t47d_stat3_veh-X-t47d_stat3_veh_input_peaks.narrowPeak.gz |
63.4 Kb |
(ftp)(http) |
NARROWPEAK |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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