ArticleThe Journal of clinical investigation2019
Chromatin remodeling ATPase BRG1 and PTEN are synthetic lethal in prostate cancer.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 88 citations in OpenAlex.
- CHD6 promotes triple-negative breast cancer progression and is associated with PI3K/AKT and MAPK pathways.International journal of clinical oncology · 2026Article
- Osimertinib Resistance in EGFR-Mutated Non-Small Cell Lung Cancer: Mechanisms and Therapeutic Strategies.MedComm · 2026Review
- Loss of Brg1 prevents the progression of pulmonary hypertension by inhibiting Nrf2 expression.Scientific reports · 2026Article
- Review
- A Double-Negative Prostate Cancer Subtype Is Vulnerable to SWI/SNF-Targeting Degrader Molecules.Cancer research · 2026Article
- Acetyl-coenzyme A synthetase 2-mediated acetyl-coenzyme A accumulation promotes mitophagy and tumor growth via increased H3K27ac in hepatitis B virus-related hepatocellular carcinoma.Clinical and molecular hepatology · 2026Article
- Transcriptional and epigenetic reprogramming, lineage plasticity and therapy resistance in prostate cancer.Journal of the National Cancer Center · 2026Review
- BRG1 orchestrates diabetic corneal neuropathy via PI3K/AKT-mediated glycolytic reprogramming.Eye and vision (London, England) · 2026Article
- Cancer and Aging Biomarkers: Classification, Early Detection Technologies and Emerging Research Trends.Biosensors · 2025Review
- Review
- A double-negative prostate cancer subtype is vulnerable to SWI/SNF-targeting degrader molecules.bioRxiv : the preprint server for biology · 2025Article
- Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Prostate cancer epigenetics - from pathophysiology to clinical application.Nature reviews. Urology · 2025Review
- YTHDF1/RNF7/p27 axis promotes prostate cancer progression.Cell death & disease · 2025Article
- Synthetic lethality in cancer: a protocol for scoping review of gene interactions from synthetic lethal screens and functional studies.Systematic reviews · 2025Article
- Loss of ARID1A accelerates prostate tumourigenesis with a proliferative collagen-poor phenotype through co-operation with AP1 subunit cFos.British journal of cancer · 2025Article
- Identification of selective SWI/SNF dependencies in enzalutamide-resistant prostate cancer.Communications biology · 2025Article
- BRG1 promotes liver cancer cell proliferation and metastasis by enhancing mitochondrial function and ATP5A1 synthesis through TOMM40.Cancer biology & therapy · 2024Article
- Tumor suppressors RBL1 and PTEN are epigenetically silenced in IPF mesenchymal progenitor cells by a CD44/Brg1/PRMT5 regulatory complex.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- CRISPR/Cas9 Technology Providing the Therapeutic Landscape of Metastatic Prostate Cancer.Pharmaceuticals (Basel, Switzerland) · 2024Review
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Loss of phosphatase and tensin homolog (PTEN) represents one hallmark of prostate cancer (PCa). However, restoration of PTEN or inhibition of the activated PI3K/AKT pathway has shown limited success, prompting us to identify obligate targets for disease intervention. We hypothesized that PTEN loss might expose cells to unique epigenetic vulnerabilities. Here, we identified a synthetic lethal relationship between PTEN and Brahma-related gene 1 (BRG1), an ATPase subunit of the SWI/SNF chromatin remodeling complex. Higher BRG1 expression in tumors with low PTEN expression was associated with a worse clinical outcome. Genetically engineered mice (GEMs) and organoid assays confirmed that ablation of PTEN sensitized the cells to BRG1 depletion. Mechanistically, PTEN loss stabilized BRG1 protein through the inhibition of the AKT/GSK3β/FBXW7 axis. Increased BRG1 expression in PTEN-deficient PCa cells led to chromatin remodeling into configurations that drove a protumorigenic transcriptome, causing cells to become further addicted to BRG1. Furthermore, we showed in preclinical models that BRG1 antagonist selectively inhibited the progression of PTEN-deficient prostate tumors. Together, our results highlight the synthetic lethal relationship between PTEN and BRG1 and support targeting BRG1 as an effective approach to the treatment of PTEN-deficient PCa.
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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 OpenQuestion graph.