ArticleBritish journal of cancer2021
Insulin receptor substrate-1 (IRS-1) mediates progesterone receptor-driven stemness and endocrine resistance in oestrogen receptor+ breast cancer.
Article in British journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 32 citations in OpenAlex.
- Progesterone receptors drive advanced breast cancer phenotypes including circulating tumor- and stem-like cell expansion in the context of ESR1 mutation.NPJ breast cancer · 2026Article
- Association between insulin resistance and breast cancer risk in perimenopausal and postmenopausal women: mediating effects of oxidative stress and inflammatory biomarkers.International journal of surgery (London, England) · 2025Article
- Progesterone receptors drive advanced breast cancer phenotypes including circulating tumor- and stem-like cell expansion in the context ofbioRxiv : the preprint server for biology · 2025Article
- Bioinformatic Characterization of Genes That Are Correlated to the Progression of Breast Cancer to Breast Cancer Brain Metastasis.Cancer reports (Hoboken, N.J.) · 2025Article
- Proteogenomic characterization of invasive breast tumors in young women.NPJ breast cancer · 2025Article
- Emerging Mechanisms of Therapy Resistance in Metastatic ER+ Breast Cancer.Endocrinology · 2025Review
- Isoform-Specific Gene Regulation by Progesterone Receptors Drives Divergent Phenotypes in Breast Cancer Cells.bioRxiv : the preprint server for biology · 2025Article
- Progesterone Receptor Signaling Promotes Cancer Associated Fibroblast Mediated Tumorigenicity in ER+ Breast Cancer.Endocrinology · 2024Article
- Bisphenol-A in Drinking Water Accelerates Mammary Cancerogenesis and Favors an Immunosuppressive Tumor Microenvironment in BALB-International journal of molecular sciences · 2024Article
- Metabolic underpinnings of cancer-related fatigue.American journal of physiology. Endocrinology and metabolism · 2024Review
- Dynamic interplay of nuclear receptors in tumor cell plasticity and drug resistance: Shifting gears in malignant transformations and applications in cancer therapeutics.Cancer metastasis reviews · 2024Review
- Synergy between PEDF and Doxorubicin in Breast Cancer Cells: Effects on Metastatic and Metabolic Pathways.International journal of molecular sciences · 2024Article
- ERα/PR crosstalk is altered in the context of the ERα Y537S mutation and contributes to endocrine therapy-resistant tumor proliferation.NPJ breast cancer · 2023Article
- Comparison Study of Small Extracellular Vesicle Isolation Methods for Profiling Protein Biomarkers in Breast Cancer Liquid Biopsies.International journal of molecular sciences · 2023Article
- Identification of a novel ER-NFĸB-driven stem-like cell population associated with relapse of ER+ breast tumors.Breast cancer research : BCR · 2022Article
- The Insulin-like Growth Factor Signaling Pathway in Breast Cancer: An Elusive Therapeutic Target.Life (Basel, Switzerland) · 2022Review
- Membrane-Initiated Estrogen, Androgen, and Progesterone Receptor Signaling in Health and Disease.Endocrine reviews · 2022Review
- Estrogen Receptor-Regulated Gene Signatures in Invasive Breast Cancer Cells and Aggressive Breast Tumors.Cancers · 2022Article
- Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor.Nature communications · 2022Article
- Selective pressure of endocrine therapy activates the integrated stress response through NFκB signaling in a subpopulation of ER positive breast cancer cells.Breast cancer research : BCR · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundProgesterone receptors (PR) are potent modifiers of endocrine responses. In aberrant signalling cancer contexts, phosphorylation events dramatically alter steroid hormone receptor action.
methodsThe transcriptomes of primary tumours and metastases in mice harbouring ER+ breast cancer patient-derived xenografts (PDXs) were analysed following single-cell RNAseq. In vitro assays were employed to delineate mechanisms of endocrine resistance and stemness.
resultsA 16-gene phospho-Ser294 PR (p-PR) signature predicted poor outcome in ER+ breast cancer. Relative to primary PDX tumours, metastatic lesions expressed abundant p-PR and exhibited an activated PR gene programme with elevated expression of PGR and IRS-1. Breast cancer models of activated PR lost the expression of IGF1R and acquired insulin hypersensitivity with tamoxifen insensitivity. Activated p-PR+ breast cancer cells formed increased tumourspheres with enlarged ALDH+ and CD24-/CD44 populations. E2 induced PR/IRS-1 interaction and exchange of IGF1Rβ for IRS-1 in p-PR-containing transcriptional complexes. Inhibition of IRS-1 or IR and inducible IRS-1 knockdown reduced tumourspheres. Endocrine-resistant models of luminal B breast cancer induced p-PR in 3D cultures and required PR and IRS-1 for tumoursphere formation.
conclusionsPhospho-PR-B cooperates with IRS-1 to promote outgrowth of endocrine-resistant and stem-like breast cancer cells. Targeting phospho-PR/IRS-1 crosstalk may block the emergence of endocrine resistance.
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