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

Autor: Jason S. Carroll, Stacey E. P. Joosten, Rasmus Siersbæk, Andrew R. Green, Wilbert Zwart, Danya Cheeseman, Igor Chernukhin, Emad A. Rakha, Rebecca Broome, Evangelia K. Papachristou, Sankari Nagarajan, Soleilmane Omarjee, Ruben Alvarez-Fernandez, Valentina Scabia, Julia P. G. Jones, Clive D'Santos, Kamal Kishore, Simon J Johnston, Sanjeev Kumar, Silvia Glont, Cathrin Brisken, Alasdair Russell, Sarah J. Aitken
Přispěvatelé: Chemical Biology, Kumar, Sanjeev [0000-0001-6017-1117], Aitken, Sarah [0000-0002-1897-4140], Kishore, Kamal [0000-0002-4650-8745], Carroll, Jason [0000-0003-3643-0080], Apollo - University of Cambridge Repository
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
pioneer factor
Cancer Research
Estrogen receptor
Kaplan-Meier Estimate
Mice
SCID
SDG 3 – Goede gezondheid en welzijn
Metastasis
STAT3
mouse intraductal xenograft model
0302 clinical medicine
Breast cancer
Mice
Inbred NOD
Neoplasm Metastasis
skin and connective tissue diseases
Fulvestrant
Cancer
Mice
Knockout
3. Good health
Gene Expression Regulation
Neoplastic
Enhancer Elements
Genetic
Oncology
030220 oncology & carcinogenesis
MCF-7 Cells
Female
Signal transduction
medicine.drug
Signal Transduction
estrogen receptor
STAT3 Transcription Factor
Antineoplastic Agents
Hormonal
Breast Neoplasms
Biology
03 medical and health sciences
breast cancer
SDG 3 - Good Health and Well-being
medicine
Animals
Humans
metastasis
Interleukin-6
Gene Expression Profiling
Estrogen Receptor alpha
medicine.disease
Xenograft Model Antitumor Assays
IL6
030104 developmental biology
Cancer research
enhancers
FOXA1
Estrogen receptor alpha
Zdroj: Cancer Cell, 38(3), 412-423.e9. Cell Press
Cancer Cell
Nagarajan, S 2020, ' IL6/STAT3 Signaling Hijacks Estrogen Receptor α Enhancers to Drive Breast Cancer Metastasis ', Cancer Cell, vol. 38, no. 3, pp. 412-423.e9 . https://doi.org/10.1016/j.ccell.2020.06.007
ISSN: 1535-6108
DOI: 10.1016/j.ccell.2020.06.007
Popis: 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.
Databáze: OpenAIRE
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