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IL6/JAK/STAT3-mediated crosstalk between cancer associated fibroblasts and epithelial cells promotes lineage plasticity and prostate cancer progression.

ABSTRACT: IL6/JAK/STAT3-mediated crosstalk between cancer associated fibroblasts and epithelial cells promotes lineage plasticity and prostate cancer progression.

PROVIDER: PRJNA988480 | 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/JAK/STAT3-mediated crosstalk between cancer associated fibroblasts and epithelial cells promotes lineage plasticity and prostate cancer progression [scRNA-seq]

Project description:IL6/JAK/STAT3-mediated crosstalk between cancer associated fibroblasts and epithelial cells promotes lineage plasticity and prostate cancer progression [scRNA-seq]

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IL6/JAK/STAT3-mediated crosstalk between cancer associated fibroblasts and epithelial cells promotes lineage plasticity and prostate cancer progression [scATAC-seq]

Project description:IL6/JAK/STAT3-mediated crosstalk between cancer associated fibroblasts and epithelial cells promotes lineage plasticity and prostate cancer progression [scATAC-seq]

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An IL6-STAT3-MR-FGF21 Axis Mediates Heart-Liver Crosstalk after Myocardial Infarction

Project description:The liver plays a protective role in myocardial infarction (MI). However, very little is known about the mechanisms. Here, we identify mineralocorticoid receptor (MR) as a pivotal nexus that conveys communications between the liver and the heart during MI. On one hand, hepatocyte MR deficiency and MR antagonist spironolactone both improve cardiac repair after MI through regulation on hepatic fibroblast growth factor 21 (FGF21), illustrating an MR/FGF21 axis that underlies the liver-to-heart protection against MI. On the other hand, an upstreaming acute interleukin-6 (IL6) / signal transducer and activator of transcription 3 (STAT3) pathway transmits the heart-to-liver signal to suppress MR expression after MI. Hepatocyte IL6 receptor (IL6R) deficiency and STAT3 deficiency both aggravate cardiac injury through their regulation on the MR/FGF21 axis. Therefore, we have unveiled an IL6/STAT3/MR/FGF21 signaling axis that mediates heart-liver crosstalk during MI. Targeting the signaling axis and the crosstalk may provide novel strategies to treat MI and heart failure.

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IL6/JAK/STAT3-mediated crosstalk between cancer associated fibroblasts and epithelial cells promotes lineage plasticity and prostate cancer progression [scRNA-seq]

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IL6/JAK/STAT3-mediated crosstalk between cancer associated fibroblasts and epithelial cells promotes lineage plasticity and prostate cancer progression [scATAC-seq]

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

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