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IL6/STAT3 Signaling Hijacks Estrogen Receptor α Enhancers to Drive Breast Cancer Metastasis.
Siersbæk, 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; D'Santos, Clive; Zwart, Wilbert; Russell, Alasdair; Brisken, Cathrin; Carroll, Jason S.
Afiliación
  • Siersbæk R; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK. Electronic address: siersbaek@bmb.sdu.dk.
  • Scabia V; ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
  • Nagarajan S; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Chernukhin I; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Papachristou EK; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Broome R; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Johnston SJ; Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK.
  • Joosten SEP; Division of Oncogenomics, Oncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • Green AR; Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK.
  • Kumar S; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK; Addenbrookes Hospital, Cambridge CB2 0QQ, UK.
  • Jones J; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Omarjee S; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Alvarez-Fernandez R; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Glont S; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Aitken SJ; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK; Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
  • Kishore K; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Cheeseman D; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Rakha EA; Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK.
  • D'Santos C; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Zwart W; Division of Oncogenomics, Oncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands; Laboratory of Chemical Biology and Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
  • Russell A; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Brisken C; ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
  • Carroll JS; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK. Electronic address: jason.carroll@cruk.cam.ac.uk.
Cancer Cell ; 38(3): 412-423.e9, 2020 09 14.
Article en En | MEDLINE | ID: mdl-32679107
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Transducción de Señal / Elementos de Facilitación Genéticos / Interleucina-6 / Receptor alfa de Estrógeno / Factor de Transcripción STAT3 Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2020 Tipo del documento: Article
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Transducción de Señal / Elementos de Facilitación Genéticos / Interleucina-6 / Receptor alfa de Estrógeno / Factor de Transcripción STAT3 Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2020 Tipo del documento: Article