ArticleMolecular cancer research : MCR2020
Loss of SWI/SNF Chromatin Remodeling Alters NRF2 Signaling in Non-Small Cell Lung Carcinoma.
Article in Molecular cancer research : MCR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Clinicopathological characteristics of patients with inoperable non-small cell lung cancer harboring circulating NRF2 pathway mutations.The Journal of pathology · 2026Article
- SMARCA4/2 loss reduces BCL-xL expression and confers a druggable MCL1 dependency in cancer.NPJ precision oncology · 2026Article
- NMR and proteomic analysis of Cornus officinalis extract reveals abundance of 5-hydroxymethylfurfural and induced expression of Nrf2 and superoxide dismutase-2 in 1.1B4 human pancreatic β-cells and murine islets.Molecular and cellular endocrinology · 2026Article
- Integrative analysis of KEAP1/NFE2L2 alterations across 3600+ tumors reveals an NRF2 expression signature as a prognostic biomarker in cancer.NPJ precision oncology · 2025Article
- The role of SMARCA4 in lung cancer.Scientific reports · 2025Review
- Targeting epigenetic and post-translational modifications of NRF2: key regulatory factors in disease treatment.Cell death discovery · 2025Review
- A phase II trial of mTORC1/2 inhibition in STK11 deficient non small cell lung cancer.NPJ precision oncology · 2025Article
- SWI/SNF Complex Connects Signaling and Epigenetic State in Cells of Nervous System.Molecular neurobiology · 2025Review
- Efficacy of glutathione inhibitor eprenetapopt against the vulnerability of glutathione metabolism in SMARCA4-, SMARCB1- and PBRM1-deficient cancer cells.Scientific reports · 2024Article
- Genome-Wide CRISPR Screen Identifies KEAP1 Perturbation as a Vulnerability of ARID1A-Deficient Cells.Cancers · 2024Article
- The role of ferroptosis in cardio-oncology.Archives of toxicology · 2024Review
- Metabolic reprogramming by histone deacetylase inhibition preferentially targets NRF2-activated tumors.Cell reports · 2024Article
- ARID1A loss is associated with increased NRF2 signaling in human head and neck squamous cell carcinomas.PloS one · 2024Article
- Proximity proteomic analysis of the NRF family reveals the Parkinson's disease protein ZNF746/PARIS as a co-complexed repressor of NRF2.Science signaling · 2023Article
- Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer.Cancer cell · 2023Article
- The SWI/SNF chromatin-remodeling subunit DPF2 facilitates NRF2-dependent antiinflammatory and antioxidant gene expression.The Journal of clinical investigation · 2023Article
- Efficacy of PD-(L)1 blockade monotherapy compared with PD-(L)1 blockade plus chemotherapy in first-line PD-L1-positive advanced lung adenocarcinomas: a cohort study.Journal for immunotherapy of cancer · 2023Article
- Clinicopathologic and Genomic Factors Impacting Efficacy of First-Line Chemoimmunotherapy in Advanced NSCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2023Article
- Pathological implications of metabolic reprogramming and its therapeutic potential in medulloblastoma.Frontiers in cell and developmental biology · 2022Review
- Epigenetics alternation in lung fibrosis and lung cancer.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
The NF-E2-related factor 2 (referred to as NRF2) transcription factor binds antioxidant responsive elements within the promoters of cytoprotective genes to induce their expression. Next-generation sequencing studies in lung cancer have shown a significant number of activating mutations within the NRF2 signaling pathway. Mutations in components of the SWI/SNF chromatin-remodeling complex, a general regulator of transcription using either BRG1 or BRM as the catalytic subunit, also frequently occur in lung cancers. Importantly, low BRG1 expression levels in primary human NSCLC correlated with increased NRF2-target gene expression. Here, we show that loss of SWI/SNF complex function activated a subset of NRF2-mediated transcriptional targets. Using a series of isogenic NSCLC lines with reduced or depleted BRG1 and/or BRM expression, we observed significantly increased expression of the NRF2-target genes HMOX1 and GSTM4. In contrast, expression of the NRF2 target genes NQO1 and GCLM modestly increased following BRM reduction. Chromatin immunoprecipitation showed that BRG1 knockdown led to increased NRF2 binding at its respective ARE sites in the HMOX1 promoter but not in NQO1 and GCLM. Our data demonstrate that loss of BRG1 or BRM in lung cancer results in activation of the NRF2/KEAP1 pathway and HMOX1 expression. Therefore, we provide an additional molecular explanation for why patients harboring BRG1 or BRM mutations show poor prognoses. A better understanding of this mechanism may yield novel insights into the design of targeted treatment modalities. IMPLICATIONS: Our study identifies a novel mechanism for how mutations in the SMARCA4 gene may drive progression of human lung adenocarcinomas.
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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.