ArticleBreast cancer research : BCR2013
Oestrogen increases the activity of oestrogen receptor negative breast cancer stem cells through paracrine EGFR and Notch signalling.
Article in Breast cancer research : BCR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 98 citations in OpenAlex.
- Emerging Mechanisms of Therapy Resistance in Metastatic ER+ Breast Cancer.Endocrinology · 2025Review
- Review
- Signaling pathway dysregulation in breast cancer.Oncotarget · 2025Review
- Navigating the Intricacies of Tumor Heterogeneity: An Insight into Potential Prognostic Breast Cancer Biomarkers.Biomarker insights · 2024Review
- Leptin: A Heavyweight Player in Obesity-Related Cancers.Biomolecules · 2023Review
- Hypoxia: syndicating triple negative breast cancer against various therapeutic regimens.Frontiers in oncology · 2023Review
- The complex nature of heterogeneity and its roles in breast cancer biology and therapeutic responsiveness.Frontiers in endocrinology · 2023Review
- Identification of a novel ER-NFĸB-driven stem-like cell population associated with relapse of ER+ breast tumors.Breast cancer research : BCR · 2022Article
- Unexplored Functions of Sex Hormones in Glioblastoma Cancer Stem Cells.Endocrinology · 2022Review
- Research progress in breast cancer stem cells: characterization and future perspectives.American journal of cancer research · 2022Review
- Mammary Development and Breast Cancer: a Notch Perspective.Journal of mammary gland biology and neoplasia · 2021Review
- Patient-derived scaffolds as a drug-testing platform for endocrine therapies in breast cancer.Scientific reports · 2021Article
- NOTCH and EZH2 collaborate to repress PTEN expression in breast cancer.Communications biology · 2021Article
- Unlocking the Secrets of Cancer Stem Cells with γ-Secretase Inhibitors: A Novel Anticancer Strategy.Molecules (Basel, Switzerland) · 2021Review
- Nuclear Mechanisms Involved in Endocrine Resistance.Frontiers in oncology · 2021Review
- Notch Signalling in Breast Development and Cancer.Frontiers in cell and developmental biology · 2021Review
- Carcinoma-Associated Fibroblasts Promote Growth of Sox2-Expressing Breast Cancer Cells.Cancers · 2020Article
- AMPK Activation by Metformin Promotes Survival of Dormant ERClinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- miR-27a ameliorates chemoresistance of breast cancer cells by disruption of reactive oxygen species homeostasis and impairment of autophagy.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- The Breast Cancer Stem Cells Traits and Drug Resistance.Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
introductionAlthough oestrogen is essential for the development of the normal breast, adult mammary stem cells are known to be oestrogen receptor alpha (ER) negative and rely on paracrine signals in the mammary epithelium for mediation of developmental cues. However, little is known about how systemic oestrogen regulates breast cancer stem cell (CSC) activity.
methodsHere, we tested the effects of oestrogen on CSC activity in vitro and in vivo and investigated which paracrine signalling pathways locally mediate oestrogen effects.
resultsCSC-enriched populations (ESA+CD44+CD24low) sorted from ER positive patient derived and established cell lines have low or absent ER expression. However, oestrogen stimulated CSC activity demonstrated by increased mammosphere and holoclone formation in vitro and tumour formation in vivo. This effect was abrogated by the anti-oestrogen tamoxifen or ER siRNA. These data suggest that the oestrogen response is mediated through paracrine signalling from non-CSCs to CSCs. We have, therefore, investigated both epidermal growth factor (EGF) and Notch receptor signals downstream of oestrogen. We demonstrate that gefitinib (epidermal growth factor receptor (EGFR) inhibitor) and gamma secretase inhibitors (Notch inhibitor) block oestrogen-induced CSC activity in vitro and in vivo but GSIs more efficiently reduce CSC frequency.
conclusionsThese data establish that EGF and Notch receptor signalling pathways operate downstream of oestrogen in the regulation of ER negative CSCs.
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