| Literature DB >> 32679107 |
Rasmus Siersbæk1, Valentina Scabia2, Sankari Nagarajan3, Igor Chernukhin3, Evangelia K Papachristou3, Rebecca Broome3, Simon J Johnston4, Stacey E P Joosten5, Andrew R Green4, Sanjeev Kumar6, Julia Jones3, Soleilmane Omarjee3, Ruben Alvarez-Fernandez3, Silvia Glont3, Sarah J Aitken7, Kamal Kishore3, Danya Cheeseman3, Emad A Rakha4, Clive D'Santos3, Wilbert Zwart8, Alasdair Russell3, Cathrin Brisken2, Jason S Carroll9.
Abstract
The cytokine interleukin-6 (IL6) and its downstream effector STAT3 constitute a key oncogenic pathway, which has been thought to be functionally connected to estrogen receptor α (ER) in breast cancer. We demonstrate that IL6/STAT3 signaling drives metastasis in ER+ breast cancer independent of ER. STAT3 hijacks a subset of ER enhancers to drive a distinct transcriptional program. Although these enhancers are shared by both STAT3 and ER, IL6/STAT3 activity is refractory to standard ER-targeted therapies. Instead, inhibition of STAT3 activity using the JAK inhibitor ruxolitinib decreases breast cancer invasion in vivo. Therefore, IL6/STAT3 and ER oncogenic pathways are functionally decoupled, highlighting the potential of IL6/STAT3-targeted therapies in ER+ breast cancer. CrownEntities:
Keywords: FOXA1; IL6; STAT3; breast cancer; estrogen receptor; metastasis; mouse intraductal xenograft model; pioneer factor
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Year: 2020 PMID： 32679107 PMCID： PMC7116707 DOI： 10.1016/j.ccell.2020.06.007
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743