ArticleProstate cancer and prostatic diseases2021
BRD4 regulates key transcription factors that drive epithelial-mesenchymal transition in castration-resistant prostate cancer.
Article in Prostate cancer and prostatic diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Systematic investigation of zinc finger MYND-type containing 11-mediated alternative splicing reveals notable events in prostate cancer.Asian journal of urology · 2026Article
- Epigenetic reprogramming as the nexus of cancer stemness and therapy resistance: implications for biomarker discovery.Discover oncology · 2025Review
- New frontiers in prostate cancer treatment from systemic therapy to targeted therapy.EMBO molecular medicine · 2025Review
- BRD4 Mediates Transforming Growth Factor-β-Induced Smooth Muscle Cell Differentiation from Mesenchymal Progenitor Cells.International journal of molecular sciences · 2025Article
- Androgen-induced AR-BRD4 transcriptional regulatory complex promotes malignant proliferation of osteosarcoma cells.Cell death discovery · 2025Article
- Phosphorylation by JNK switches BRD4 functions.Molecular cell · 2024Article
- Characterization and Experimental Use of Multiple Myeloma Bone Marrow Endothelial Cells and Progenitors.International journal of molecular sciences · 2024Article
- Targeting BRD4: Potential therapeutic strategy for head and neck squamous cell carcinoma (Review).Oncology reports · 2024Article
- Targeting Key Players of Neuroendocrine Differentiation in Prostate Cancer.International journal of molecular sciences · 2023Review
- Review
- BET Bromodomain Inhibitors: Novel Design Strategies and Therapeutic Applications.Molecules (Basel, Switzerland) · 2023Review
- Role of transcription factors and chromatin modifiers in driving lineage reprogramming in treatment-induced neuroendocrine prostate cancer.Frontiers in cell and developmental biology · 2023Review
- Consistent DNA Hypomethylations in Prostate Cancer.International journal of molecular sciences · 2022Article
- Novel plasma exosome biomarkers for prostate cancer progression in co-morbid metabolic disease.Advances in cancer biology - metastasis · 2022Article
- Roles of Bromodomain Extra Terminal Proteins in Metabolic Signaling and Diseases.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Novel forms of prostate cancer chemoresistance to successful androgen deprivation therapy demand new approaches: Rationale for targeting BET proteins.The Prostate · 2022Review
- Review
- Identification of bromodomain-containing proteins prognostic value and expression significance based on a genomic landscape analysis of ovarian serous cystadenocarcinoma.Frontiers in oncology · 2022Article
- Transcription Factors as Novel Therapeutic Targets and Drivers of Prostate Cancer Progression.Frontiers in oncology · 2022Review
- Overcoming Cancer Drug Resistance Utilizing PROTAC Technology.Frontiers in cell and developmental biology · 2022Review
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundAndrogen deprivation therapies for the hormone-dependent stages of prostate cancer have become so effective that new forms of chemoresistant tumors are emerging in clinical practice, and require new targeted therapies in the metastatic setting. Yet there are important gaps in our understanding of the relevant transcriptional networks driving this process. Progression from localized to metastatic castration resistant prostate cancer (mCRPC) occurs as a result of accumulated resistance mechanisms that develop upon sustained androgen receptor (AR) suppression. Critical to this progression is the plastic nature by which prostate tumor cells transition from epithelial to mesenchymal states (EMT).
methodsHere, using prostate cancer cell lines with different AR composition, we systematically manipulated somatic proteins of the Bromodomain and ExtraTerminal (BET) family (BRD2, BRD3, and BRD4) to determine which BET proteins influence EMT. We used the TCGA repository to correlate the expression of individual BET genes with key EMT genes and determined biochemical recurrence in 414 patients and progression free survival in 488 patients.
resultsWe found that only BRD4-and not BRD2 or BRD3-regulates the expression of SNAI1 and SNAI2, and that the downregulation of these EMT transcription factors significantly increases E-cadherin expression. Furthermore, of the BET genes, only BRD4 correlates with survival outcomes in prostate cancer patients. Moreover, selective degradation of BRD4 protein with MZ1 ablates EMT (transcriptionally and morphologically) induced by TGFß signaling.
conclusionsMany relapsed/refractory tumors share a neuroendocrine transcriptional signature that had been relatively rare until highly successful antiandrogen drugs like abiraterone and enzalutamide came into widespread use. New therapeutic targets must therefore be developed. Our results identify key EMT genes regulated by BRD4, and offers a novel druggable target to treat mCRPC. BRD4-selective protein degraders offer a promising next generation approach to treat the emerging forms of chemoresistance in advanced prostate cancer.
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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 OpenQuestion graph.