{"entity": "publication", "iuid": "e6cf6e6114524941be23f5d222043fe4", "timestamp": "2026-09-28T06:36:10.173Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e6cf6e6114524941be23f5d222043fe4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e6cf6e6114524941be23f5d222043fe4"}}, "title": "Cancer-associated fibroblasts rewire the estrogen receptor response in luminal breast cancer, enabling estrogen independence.", "authors": [{"family": "Reid", "given": "Steven E", "initials": "SE"}, {"family": "Pantaleo", "given": "Jessica", "initials": "J"}, {"family": "Bolivar", "given": "Paulina", "initials": "P"}, {"family": "Bocci", "given": "Matteo", "initials": "M", "orcid": "0000-0002-8774-0006", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5c3968f94ce344cc8c8189e1d469432c.json"}}, {"family": "Sj\u00f6lund", "given": "Jonas", "initials": "J", "orcid": "0000-0002-6992-3415", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/66ef1f7efe9941f9b4d9ef0b890f5385.json"}}, {"family": "Morsing", "given": "Mikkel", "initials": "M", "orcid": "0000-0001-8322-8796", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d44ffc97225c4d6d939c8b552869f3ce.json"}}, {"family": "Cordero", "given": "Eugenia", "initials": "E"}, {"family": "Larsson", "given": "Sara", "initials": "S", "orcid": "0000-0002-0002-0779", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2442e97082a442878b3a2e161f10a605.json"}}, {"family": "Malmberg", "given": "Maria", "initials": "M"}, {"family": "Seashore-Ludlow", "given": "Brinton", "initials": "B"}, {"family": "Pietras", "given": "Kristian", "initials": "K", "orcid": "0000-0001-6738-4705", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5c29a7ab65c34459a6ab014663c59f05.json"}}], "type": "journal article", "published": "2024-04-00", "journal": {"title": "Oncogene", "issn": "1476-5594", "volume": "43", "issue": "15", "pages": "1113-1126", "issn-l": "0950-9232"}, "abstract": "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)-\u03b1 expression and activity in luminal breast tumors. Notably, CAFs mediated estrogen-independent tumor growth by selectively regulating ER-\u03b1 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-\u03b1 signaling. Among these, the Transforming Growth Factor-\u03b2 and the Janus kinase signaling cascades were validated as actionable targets to counteract the CAF-induced modulation of ER-\u03b1 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-\u03b1 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.", "doi": "10.1038/s41388-024-02973-x", "pmid": "38388711", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10997519"}, {"db": "pii", "key": "10.1038/s41388-024-02973-x"}], "notes": [], "created": "2026-09-23T09:03:17.132Z", "modified": "2026-09-23T09:03:17.427Z"}