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We are analyzing https://www.nature.com/articles/s41416-020-01094-y.

Title:
Insulin receptor substrate-1 (IRS-1) mediates progesterone receptor-driven stemness and endocrine resistance in oestrogen receptor+ breast cancer | British Journal of Cancer
Description:
Progesterone receptors (PR) are potent modifiers of endocrine responses. In aberrant signalling cancer contexts, phosphorylation events dramatically alter steroid hormone receptor action. The 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. A 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. Phospho-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.
Website Age:
30 years and 1 months (reg. 1994-08-11).

Matching Content Categories {📚}

  • Science
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Content Management System {📝}

What CMS is nature.com built with?

Custom-built

No common CMS systems were detected on Nature.com, and no known web development framework was identified.

Traffic Estimate {📈}

What is the average monthly size of nature.com audience?

🌆 Monumental Traffic: 20M - 50M visitors per month


Based on our best estimate, this website will receive around 21,169,014 visitors per month in the current month.

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How Much Does Nature.com Make? {💰}


Display Ads {🎯}

Display Ads ~ $203,300 per month
According to our algorithms, Nature.com's monthly online income from display advertising ranges from $135,514 to $372,663.

Keywords {🔍}

cancer, breast, cells, pubmed, irs, article, prb, cas, fig, google, scholar, cell, receptor, expression, models, phosphopr, mcf, insulin, gene, central, target, resistance, tumoursphere, data, tamr, genes, progesterone, endocrine, signalling, tumours, tamoxifen, formation, expressing, nature, metastatic, treatment, usa, levels, primary, pdx, tumourspheres, igfrβ, growth, supplementary, receptors, lesions, activity, protein, previously, relative,

Topics {✒️}

nature portfolio author information authors goat anti-rabbit igg-hrp breast cancer research goat anti-mouse igg-hrp sumo-deficient/phospho-mimic pr phospho-pr-specific gene signatures dextran-coated charcoal-stripped fbs prognostic index nature 523 nature 540 nature target phospho-pr-specific signalling stress-sensing protein kinases real-time quantitative pcr standard light/dark cycle mitogen-activated protein kinase 10 μm paraffin sections reprints key er/pr-binding partner irs-1/phospho-pr target genes single-cell phospho-pr levels er/pr/c-src complexes anti-rabbit ig mp-7401 metastasis nod/scid/iliirg−/− er-positive breast cancer er+ breast tumors svetlana estrogen receptor-alpha regulates endocrine-resistant breast cancer targeting phospho-pr/irs-1 crosstalk robust phospho-pr staining anti-mouse ig mp-7402 er/ps294-pr/irs-1 complexes phospho-pr gene signature specific pathogen-free housing data linking phospho-pr ultra-low attachment plates ultra-low attachment dishes references siegel igf1rβ/ir hybrid receptors plenti cmv-neo vector er-nfĸb-driven stem cyclin-dependent kinase 4/6 phospho-pr target genes 16-gene phospho-ser294 pr advanced breast cancer 1 ml phosphate-buffered saline phenol red-free imem author correspondence original author

Schema {🗺️}

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         headline:Insulin receptor substrate-1 (IRS-1) mediates progesterone receptor-driven stemness and endocrine resistance in oestrogen receptor+ breast cancer
         description:Progesterone receptors (PR) are potent modifiers of endocrine responses. In aberrant signalling cancer contexts, phosphorylation events dramatically alter steroid hormone receptor action. The 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. A 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. Phospho-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.
         datePublished:2020-11-04T00:00:00Z
         dateModified:2020-11-04T00:00:00Z
         pageStart:217
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            Epidemiology
            Molecular Medicine
            Oncology
            Drug Resistance
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      headline:Insulin receptor substrate-1 (IRS-1) mediates progesterone receptor-driven stemness and endocrine resistance in oestrogen receptor+ breast cancer
      description:Progesterone receptors (PR) are potent modifiers of endocrine responses. In aberrant signalling cancer contexts, phosphorylation events dramatically alter steroid hormone receptor action. The 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. A 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. Phospho-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.
      datePublished:2020-11-04T00:00:00Z
      dateModified:2020-11-04T00:00:00Z
      pageStart:217
      pageEnd:227
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         Breast cancer
         Cell biology
         Biomedicine
         general
         Cancer Research
         Epidemiology
         Molecular Medicine
         Oncology
         Drug Resistance
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      name:Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, USA
      name:Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, USA
      name:Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, USA
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