Rasmus Siersbaek
IL6/STAT3 Signaling Hijacks Estrogen Receptor ? Enhancers to Drive Breast Cancer Metastasis
Siersbaek, Rasmus; Scabia, Valentina; Nagarajan, Sankari; Chernukhin, Igor; Papachristou, Evangelia K; Broome, Rebecca; Johnston, Simon J; Joosten, Stacey E P; Green, Andrew R; Kumar, Sanjeev; Jones, Julia; Omarjee, Soleilmane; Alvarez-Fernandez, Ruben; Glont, Silvia; Aitken, Sarah J; Kishore, Kamal; Cheeseman, Danya; Rakha, Emad A; Santos, Clive D; Zwart, Wilbert; Russell, Alasdair; Brisken, Cathrin; Carroll, Jason S
Authors
Valentina Scabia
Sankari Nagarajan
Igor Chernukhin
Evangelia K Papachristou
Rebecca Broome
Simon J Johnston
Stacey E P Joosten
ANDREW GREEN ANDREW.GREEN@NOTTINGHAM.AC.UK
Associate Professor
Sanjeev Kumar
Julia Jones
Soleilmane Omarjee
Ruben Alvarez-Fernandez
Silvia Glont
Sarah J Aitken
Kamal Kishore
Danya Cheeseman
EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology
Clive D Santos
Wilbert Zwart
Alasdair Russell
Cathrin Brisken
Jason S Carroll
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 ? (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.
Citation
Siersbaek, R., Scabia, V., Nagarajan, S., Chernukhin, I., Papachristou, E. K., Broome, R., …Carroll, J. S. (2020). IL6/STAT3 Signaling Hijacks Estrogen Receptor α Enhancers to Drive Breast Cancer Metastasis. Cancer Cell, 38(3), 412-423.e9. https://doi.org/10.1016/j.ccell.2020.06.007
Journal Article Type | Article |
---|---|
Acceptance Date | Jun 12, 2020 |
Online Publication Date | Jul 16, 2020 |
Publication Date | Sep 14, 2020 |
Deposit Date | Jun 15, 2020 |
Publicly Available Date | Mar 29, 2024 |
Journal | Cancer Cell |
Print ISSN | 1535-6108 |
Electronic ISSN | 1878-3686 |
Publisher | Elsevier (Cell Press) |
Peer Reviewed | Peer Reviewed |
Volume | 38 |
Issue | 3 |
Pages | 412-423.e9 |
DOI | https://doi.org/10.1016/j.ccell.2020.06.007 |
Keywords | estrogen receptorSTAT3IL6breast cancermetastasisFOXA1mouse intraductal xenograft modelpioneer factor |
Public URL | https://nottingham-repository.worktribe.com/output/4655119 |
Publisher URL | https://www.sciencedirect.com/science/article/pii/S1535610820303111 |
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