ArticleNucleic acids research2022
Super-enhancer-controlled positive feedback loop BRD4/ERα-RET-ERα promotes ERα-positive breast cancer.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 61 citations in OpenAlex.
- A novel super-enhancer-related gene signature predicts prognosis and immune microenvironment for breast cancer.BMC cancer · 2023Trial
- From cell to disease: Regulatory networks and mechanisms of super‑enhancers in aging (Review).Molecular medicine reports · 2026Review
- Glucose and Glutamine Deprivation Promotes Breast Cancer Lung Metastasis via BRD4-Dependent Enhancer Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nucleic sexual hormone receptor signaling pathways in breast cancer: function regulation, crosstalk, and therapeutic implications.NPJ precision oncology · 2026Review
- Redistribution of super-enhancers promotes malignancy in human hepatocellular carcinoma.Journal of advanced research · 2026Article
- Targeting a super-enhancer induced aldehyde dehydrogenase metabolic loop mitigates CDK4/6 inhibitor resistance in estrogen receptor-positive cancers.Nature communications · 2026Article
- Optogenetic manipulation of estrogen receptor signaling to improve estrogen deficiency.iScience · 2026Article
- Superenhancers shape the landscape and repair dynamics of transcription-associated DNA breaks in cancer.Science advances · 2026Article
- BRD4 PROTAC degrader enhances fulvestrant sensitivity in ER+ breast cancer via super-enhancer associated GREB1.Frontiers in oncology · 2026Article
- Recent Advances (2020-2025) in Estrogen and ER-Positive Breast Cancer: Receptor Signaling, Tumor Microenvironment, Endocrine Therapy Resistance and Innovative Treatment Strategies-A Comprehensive Review.Cancer management and research · 2026Review
- Reprogramming oncogenic mitochondria in pancreatic adenocarcinoma through BRD4 inhibition leads to programmed cell death.The Journal of pharmacology and experimental therapeutics · 2025Article
- Harnessing artificial intelligence to identify Bufalin as a molecular glue degrader of estrogen receptor alpha.Nature communications · 2025Article
- Multi-omics based and AI-driven drug repositioning for epigenetic therapy in female malignancies.Journal of translational medicine · 2025Review
- Myocardial transcriptomic and proteomic landscapes across the menopausal continuum in a murine model of chemically induced accelerated ovarian failure.Physiological genomics · 2025Article
- Phase Separation: Orchestrating Biological Adaptations to Environmental Fluctuations.International journal of molecular sciences · 2025Review
- Zooming into Gene Activation: Estrogen Receptor α Dimerization and DNA Binding Visualized by High-Speed Atomic Force Microscopy.ACS nano · 2025Article
- MUC1-C dependency in drug resistant HR+/HER2- breast cancer identifies a new target for antibody-drug conjugate treatment.NPJ breast cancer · 2025Article
- TRAPT: a multi-stage fused deep learning framework for predicting transcriptional regulators based on large-scale epigenomic data.Nature communications · 2025Article
- Lactate accumulation induces H4K12la to activate super-enhancer-driven RAD23A expression and promote niraparib resistance in ovarian cancer.Molecular cancer · 2025Article
- Super-enhancer-hijacking RBBP7 potentiates metastasis and stemness of breast cancer via recruiting NuRD complex subunit LSD1.Journal of translational medicine · 2025Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Estrogen and estrogen receptor alpha (ERα)-induced gene transcription is tightly associated with ERα-positive breast carcinogenesis. ERα-occupied enhancers, particularly super-enhancers, have been suggested to play a vital role in regulating such transcriptional events. However, the landscape of ERα-occupied super-enhancers (ERSEs) as well as key ERα-induced target genes associated with ERSEs remain to be fully characterized. Here, we defined the landscape of ERSEs in ERα-positive breast cancer cell lines, and demonstrated that bromodomain protein BRD4 is a master regulator of the transcriptional activation of ERSEs and cognate ERα target genes. RET, a member of the tyrosine protein kinase family of proteins, was identified to be a key ERα target gene of BRD4-regulated ERSEs, which, in turn, is vital for ERα-induced gene transcriptional activation and malignant phenotypes through activating the RAS/RAF/MEK2/ERK/p90RSK/ERα phosphorylation cascade. Combination therapy with BRD4 and RET inhibitors exhibited additive effects on suppressing ERα-positive breast cancer both in vitro and in vivo, comparable with that of standard endocrine therapy tamoxifen. Furthermore, combination therapy re-sensitized a tamoxifen-resistant ERα-positive breast cancer cell line to tamoxifen treatment. Taken together, our data uncovered the critical role of a super-enhancer-associated positive feedback loop constituting BRD4/ERα-RET-ERα in ERα-positive breast cancer, and suggested that targeting components in this loop would provide a new therapeutic avenue for treating ERα-positive breast cancer in the clinic.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.