ArticleJournal of molecular cell biology2019
Glucocorticoid receptor-IRS-1 axis controls EMT and the metastasis of breast cancers.
Article in Journal of molecular cell biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- Context-dependent effect of glucocorticoid receptor activity shapes ovarian cancer cell plasticity and therapy response.Molecular cancer · 2026Article
- High level expression of glucocorticoid receptor (GR) is linked to aggressive tumor features, early biochemical recurrence, and genetic instability in prostate cancer.Prostate cancer and prostatic diseases · 2026Article
- Glucocorticoid-Mediated Skeletal Muscle Atrophy: Molecular Mechanisms and Potential Therapeutic Targets.International journal of molecular sciences · 2025Review
- Nuclear Receptors in Bladder Cancer: Insights into miRNA-Mediated Regulation and Potential Therapeutic Implications.International journal of molecular sciences · 2025Review
- Glucocorticoid Receptor (GR) Expression in Human Tumors: A Tissue Microarray Study on More than 14,000 Tumors.Biomedicines · 2025Article
- Psychological stress-activated NR3C1/NUPR1 axis promotes ovarian tumor metastasis.Acta pharmaceutica Sinica. B · 2025Article
- Glucocorticoid receptors orchestrate a convergence of host and cellular stress signals in triple negative breast cancer.The Journal of steroid biochemistry and molecular biology · 2024Review
- Glucocorticoid receptor: a harmonizer of cellular plasticity in breast cancer-directs the road towards therapy resistance, metastatic progression and recurrence.Cancer metastasis reviews · 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
- Glucocorticoid receptor regulates the epithelial-mesenchymal transition process through GR/ZEB1/E-cad and is involved in breast cancer endocrine drug resistance-a bioinformatics analysis.Translational cancer research · 2023Article
- Article
- Histone deacetylase inhibitors inhibit lung adenocarcinoma metastasis via HDAC2/YY1 mediated downregulation of Cdh1.Scientific reports · 2023Article
- Recent Advances in Transcription Factors Biomarkers and Targeted Therapies Focusing on Epithelial-Mesenchymal Transition.Cancers · 2023Review
- Biology of breast cancer brain metastases and novel therapies targeting the blood brain barrier: an updated review.Medical oncology (Northwood, London, England) · 2023Review
- Hormonal regulation of metabolism-recent lessons learned from insulin and estrogen.Clinical science (London, England : 1979) · 2023Review
- Context-Dependent Role of Glucocorticoid Receptor Alpha and Beta in Breast Cancer Cell Behaviour.Cells · 2023Article
- The Role of Glucocorticoids in Breast Cancer Therapy.Current oncology (Toronto, Ont.) · 2022Review
- Mechanisms behind context-dependent role of glucocorticoids in breast cancer progression.Cancer metastasis reviews · 2022Review
- Midkine promotes breast cancer cell proliferation and migration by upregulating NR3C1 expression and activating the NF-κB pathway.Molecular biology reports · 2022Article
- Overexpression of glucocorticoid receptor promotes the poor progression and induces cisplatin resistance through p38 MAP kinase in cervical cancer patients.American journal of cancer research · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucocorticoid receptor (GR) is involved in the transcriptional regulation of genes that are important for various biological functions, including tumor growth and metastatic progression. However, the cellular and biological effects of GR remain poorly understood. Here, we investigated the role of GR and its underlying mechanism in mediating breast cancer cell survival and metastasis. We observed that the GR levels were increased in drug-resistant breast cancer cells and in metastatic breast cancer samples. GR promoted tumor cell invasion and lung metastasis in vivo. The GR expression levels were negatively correlated with the survival rates of breast cancer patients. Both ectopic expression and knockdown of GR revealed that GR is a strong inducer of epithelial-to-mesenchymal transition (EMT), which is consistent with its effects on cell survival and metastasis. GR suppressed the expression of insulin receptor substrate 1 (IRS-1) by acting as an IRS-1 transcriptional repressor. In addition, GR has an opposite effect on the expression levels of IRS-2, indicating that GR is able to differentially regulate the IRS-1 and IRS-2 expression. The cellular and biological effects elicited by GR were consistent with the reduced levels of IRS-1 observed in cancer cells, and GR-mediated IRS-1 suppression activated the ERK2 MAP kinase pathway, which is required for GR-mediated EMT. Taken together, our results indicate that GR-IRS-1 signaling axis plays an essential role in regulating the survival, invasion, and metastasis of breast cancer cells.
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