IL6/STAT3 Signaling Hijacks Estrogen Receptor α Enhancers to Drive Breast Cancer Metastasis.

Cancer Cell
Rasmus SiersbækJason 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 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.

References

Dec 1, 1994·Protein Science : a Publication of the Protein Society·A HammacherR J Simpson
Jun 5, 2002·Genome Research·W James KentDavid Haussler
Dec 21, 2002·International Journal of Cancer. Journal International Du Cancer·Roberto SalgadoLuc Y Dirix
Sep 19, 2008·Genome Biology·Yong ZhangX Shirley Liu
May 22, 2009·Nucleic Acids Research·Timothy L BaileyWilliam S Noble
Oct 31, 2009·International Journal of Cancer. Journal International Du Cancer·Nadine A BinaiSilja Wessler
Nov 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Menno P CreyghtonRudolf Jaenisch
Dec 15, 2010·Nature Genetics·Antoni HurtadoJason S Carroll
Mar 6, 2012·Nature Methods·Ben Langmead, Steven L Salzberg
May 31, 2012·Journal of Cellular Biochemistry·Antonella De LucaNicola Normanno
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Nov 15, 2012·Cancer Research·Alison WakefieldRichard W E Clarkson
Mar 16, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anita K DunbierMitch Dowsett
Jul 23, 2013·Nature Biotechnology·Patrick D HsuFeng Zhang
Aug 21, 2013·PLoS Computational Biology·Michael LawrenceVincent J Carey
Jun 16, 2014·Bioinformatics·Zuguang GuBenedikt Brors
Oct 24, 2014·Journal of Cellular and Molecular Medicine·Clelia MadedduAntonio Macciò
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Jan 22, 2015·Nucleic Acids Research·Matthew E RitchieGordon K Smyth
Jan 27, 2015·Trends in Immunology·Jan MauerJens C Brüning
Apr 22, 2015·Nature Immunology·Christopher A Hunter, Simon A Jones
May 7, 2015·Journal of Molecular Endocrinology·Yue WangDan Wang
Jan 16, 2016·Cell Systems·Arthur LiberzonPablo Tamayo
Feb 26, 2016·Breast Cancer Research and Treatment·Mohammed A AleskandaranyEmad A Rakha
Oct 30, 2016·Regulatory Toxicology and Pharmacology : RTP·Dana L ShueyAlan Roberts
Jul 18, 2017·Expert Opinion on Investigational Drugs·Andrea L A WongBoon-Cher Goh
Dec 6, 2017·Scientific Reports·Peter BankheadPeter W Hamilton
Dec 20, 2017·Cancer Immunology, Immunotherapy : CII·Narmeen AhmadStewart G Martin
Feb 7, 2018·Nature Reviews. Clinical Oncology·Daniel E JohnsonJennifer R Grandis
Aug 18, 2018·Molecular Oncology·Margaret M CenteneraWayne D Tilley
Oct 27, 2018·Science·M Ryan CorcesHoward Y Chang

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Citations

Dec 29, 2020·Molecular Aspects of Medicine·Isabel Mayayo-PeraltaWilbert Zwart
May 18, 2021·Journal of Mammary Gland Biology and Neoplasia·Quentin JuppetDaniel Sage
Jul 6, 2021·Current Opinion in Structural Biology·Elizabeth M MartinPaul A Wade
Sep 15, 2021·The Biochemical Journal·Jocelyn F Chen, Qin Yan

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