ArticleCells2021
NR4A1 Regulates Tamoxifen Resistance by Suppressing ERK Signaling in ER-Positive Breast Cancer.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Models of Early Resistance to CDK4/6 Inhibitors Unveil Potential Therapeutic Treatment Sequencing.International journal of molecular sciences · 2025Trial
- Emerging Targeted and Multimodal Therapeutic Strategies in Breast Cancer: A Comprehensive Review.Breast cancer (Dove Medical Press) · 2026Review
- ML385 increases ferroptosis via inhibiting Nrf2/HO-1 pathway to enhances the sensitivity of MCF-7 TAMR to tamoxifen.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Single-Cell Multi-Modal Differential Analysis of the Human Neo-Cortex in HIV Infection Reveals Similarities with Hallmarks of Alzheimer's Disease.Research square · 2025Article
- Article
- The Long Non-Coding RNA MALAT1 Modulates NR4A1 Expression through a Downstream Regulatory Element in Specific Cancer Cell Types.International journal of molecular sciences · 2024Article
- UTRN as a potential biomarker in breast cancer: a comprehensive bioinformatics and in vitro study.Scientific reports · 2024Article
- Alterations of bovine nucleus pulposus cells with aging.Aging cell · 2023Article
- Identification of upregulated exosomal miRNAs between A2780 and A2780/DDP human ovarian cancer cells by high-throughput sequencing.Journal of ovarian research · 2023Article
- Network-informed discovery of multidrug combinations for ERα+/HER2-/PI3Kα-mutant breast cancer.Cellular and molecular life sciences : CMLS · 2023Article
- Ubiquitin-Specific Peptidase 8 Modulates Cell Proliferation and Induces Cell Cycle Arrest and Apoptosis in Breast Cancer by Stabilizing Estrogen Receptor Alpha.Journal of oncology · 2023Article
- Review
- The Role of Apoptotic Genes and Protein-Protein Interactions in Triple-negative Breast Cancer.Cancer genomics & proteomicsArticle
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Endocrine therapy is used to treat estrogen receptor (ER)-positive breast cancer. Tamoxifen is effective against this cancer subtype. Nonetheless, approximately 30% of patients treated with tamoxifen acquire resistance, resulting in therapeutic challenges. NR4A1 plays key roles in processes associated with carcinogenesis, apoptosis, DNA repair, proliferation, and inflammation. However, the role of NR4A1 in tamoxifen-resistant ER-positive breast cancer has not yet been elucidated. Here, we propose that NR4A1 is a promising target to overcome tamoxifen resistance. NR4A1 gene expression was downregulated in tamoxifen-resistant MCF7 (TamR) cells compared to that in MCF7 cells. Kaplan-Meier plots were used to identify high NR4A1 expression correlated with increased survival rates in patients with ER-positive breast cancer following tamoxifen treatment. Gain and loss of function experiments showed that NR4A1 restores sensitivity to tamoxifen by regulating cell proliferation, migration, invasion, and apoptosis. NR4A1 localized to the cytoplasm enhanced the expression of apoptotic factors. In silico and in vitro analyses revealed that NR4A1 enhanced responsiveness to tamoxifen by suppressing ERK signaling in ER-positive breast cancer, suggesting that the NR4A1/ERK signaling axis modulates tamoxifen resistance. These results indicate that NR4A1 could be a potential therapeutic target to overcome tamoxifen resistance in ER-positive breast cancer.
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