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Cancer-associated f...
Cancer-associated fibroblasts rewire the estrogen receptor response in luminal breast cancer, enabling estrogen independence
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- Reid, Steven E (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Centrum för preventiv livsmedelsforskning, Medicon Village,Universitetets särskilda verksamheter,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Food for Health Science Centre, Medicon Village,University Specialised Centres,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Pantaleo, Jessica (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Centrum för preventiv livsmedelsforskning, Medicon Village,Universitetets särskilda verksamheter,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Food for Health Science Centre, Medicon Village,University Specialised Centres,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Bolivar, Paulina (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Centrum för preventiv livsmedelsforskning, Medicon Village,Universitetets särskilda verksamheter,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Food for Health Science Centre, Medicon Village,University Specialised Centres,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Bocci, Matteo (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Centrum för preventiv livsmedelsforskning, Medicon Village,Universitetets särskilda verksamheter,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Food for Health Science Centre, Medicon Village,University Specialised Centres,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Sjölund, Jonas (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Centrum för preventiv livsmedelsforskning, Medicon Village,Universitetets särskilda verksamheter,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Food for Health Science Centre, Medicon Village,University Specialised Centres,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Morsing, Mikkel (author)
- Lund University,Medicon Village
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- Cordero, Eugenia (author)
- Lund University,Medicon Village
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- Larsson, Sara (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Experimentell onkologi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Experimental oncology,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Malmberg, Maria (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Centrum för preventiv livsmedelsforskning, Medicon Village,Universitetets särskilda verksamheter,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Food for Health Science Centre, Medicon Village,University Specialised Centres,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Seashore-Ludlow, Brinton (author)
- Karolinska Institutet,Karolinska Institute,Science for Life Laboratory (SciLifeLab)
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- Pietras, Kristian (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Centrum för preventiv livsmedelsforskning, Medicon Village,Universitetets särskilda verksamheter,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Food for Health Science Centre, Medicon Village,University Specialised Centres,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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(creator_code:org_t)
- 2024
- 2024
- English 14 s.
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In: Oncogene. - 1476-5594.
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Abstract
Subject headings
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- Advanced breast cancers represent a major therapeutic challenge due to their refractoriness to treatment. Cancer-associated fibroblasts (CAFs) are the most abundant constituents of the tumor microenvironment and have been linked to most hallmarks of cancer. However, the influence of CAFs on therapeutic outcome remains largely unchartered. Here, we reveal that spatial coincidence of abundant CAF infiltration with malignant cells was associated with reduced estrogen receptor (ER)-α expression and activity in luminal breast tumors. Notably, CAFs mediated estrogen-independent tumor growth by selectively regulating ER-α signaling. Whereas most prototypical estrogen-responsive genes were suppressed, CAFs maintained gene expression related to therapeutic resistance, basal-like differentiation, and invasion. A functional drug screen in co-cultures identified effector pathways involved in the CAF-induced regulation of ER-α signaling. Among these, the Transforming Growth Factor-β and the Janus kinase signaling cascades were validated as actionable targets to counteract the CAF-induced modulation of ER-α activity. Finally, genes that were downregulated in cancer cells by CAFs were predictive of poor response to endocrine treatment. In conclusion, our work reveals that CAFs directly control the luminal breast cancer phenotype by selectively modulating ER-α expression and transcriptional function, and further proposes novel targets to disrupt the crosstalk between CAFs and tumor cells to reinstate treatment response to endocrine therapy in patients.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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Oncogene
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To the university's database
- By the author/editor
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Reid, Steven E
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Pantaleo, Jessic ...
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Bolivar, Paulina
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Bocci, Matteo
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Sjölund, Jonas
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Morsing, Mikkel
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show more...
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Cordero, Eugenia
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Larsson, Sara
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Malmberg, Maria
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Seashore-Ludlow, ...
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Pietras, Kristia ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Oncogene
- By the university
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Lund University
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Karolinska Institutet