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IL6/STAT3 co-opts ER/FOXA1 regulatory elements to drive metastasis in breast cancer (RNA-Seq)

ABSTRACT: IL6/STAT3 co-opts ER/FOXA1 regulatory elements to drive metastasis in breast cancer (RNA-Seq)

PROVIDER: PRJNA518886 | ENA |

REPOSITORIES: ENA

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IL6/STAT3 co-opts ER regulatory elements to drive metastasis in breast cancer

Project description: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.

2021-09-08 | PXD012980 | Pride

IL6/STAT3 co-opts ER/FOXA1 regulatory elements to drive metastasis in breast cancer (ChIP-Seq)

2020-07-17 | GSE126004 | GEO

IL6/STAT3 co-opts ER/FOXA1 regulatory elements to drive metastasis in breast cancer [ATAC-Seq]

2020-07-17 | GSE150131 | GEO

IL6/STAT3 co-opts ER/FOXA1 regulatory elements to drive metastasis in breast cancer (RNA-Seq)

Project description: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 a positive (ER+) breast cancer, we demonstrate that IL6 increases both primary tumor growth and distant metastases. In pre-clinical models and clinical specimens, signal transducer and activator of transcription 3 (STAT3) mediates IL6-induced activation of a metastatic gene program from enhancers shared with ER and its pioneer factor FOXA1. However, STAT3 drives transcription independent of ER and FOXA1 function from these enhancers, and the IL6/STAT3 pathway is therefore resistant to ER-targeted therapies, decoupling these two important oncogenic pathways. This demonstrates that ER/FOXA1 and IL6/STAT3 are two parallel, but functionally independent and actionable pathways controlling breast cancer progression.

2020-07-17 | GSE126003 | GEO

IL6/STAT3 co-opts ER/FOXA1 regulatory elements to drive metastasis in breast cancer

Project description:IL6/STAT3 co-opts ER/FOXA1 regulatory elements to drive metastasis in breast cancer

| PRJNA518884 | ENA

IL6/STAT3 co-opts ER/FOXA1 regulatory elements to drive metastasis in breast cancer (ChIP-Seq)

Project description:IL6/STAT3 co-opts ER/FOXA1 regulatory elements to drive metastasis in breast cancer (ChIP-Seq)

| PRJNA518885 | ENA

IL6/STAT3 co-opts ER/FOXA1 regulatory elements to drive metastasis in breast cancer [ATAC-Seq]

Project description:IL6/STAT3 co-opts ER/FOXA1 regulatory elements to drive metastasis in breast cancer [ATAC-Seq]

| PRJNA631243 | ENA

IL6/STAT3 co-opts ER/FOXA1 regulatory elements to drive metastasis in breast cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-07-17 | GSE126006 | GEO

IL6-STAT3 downstream targets in MCF10A/MCF10A.ErbB2* cells

Project description:Overexpression in IL6 in MCF10A vs. WT, MCF10A.ErbB2* with/without shRNA targeting STAT3 Overexpression in IL6 in MCF10A vs. WT, MCF10A.ErbB* with/without shSTAT3, duplicates, two STAT3 shRNAs

2015-09-03 | E-GEOD-62235 | biostudies-arrayexpress

IL6-STAT3 downstream targets in MCF10A/MCF10A.ErbB2* cells

Project description:Overexpression in IL6 in MCF10A vs. WT, MCF10A.ErbB2* with/without shRNA targeting STAT3

2015-09-03 | GSE62235 | GEO