ArticleNature cell biology2024
Loss of Kmt2c or Kmt2d drives brain metastasis via KDM6A-dependent upregulation of MMP3.
Article in Nature cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Molecular and Clinicopathological Biomarkers Predicting Brain Metastasis in Triple-Negative Breast Cancer: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Review
- Epigenetics in lung cancer precision medicine: from bench to bedside-a narrative review.Translational lung cancer research · 2026Review
- Loss of Kmt2c/d promotes gastric cancer and confers vulnerability to mTORC1 and PD-1 inhibition.The Journal of clinical investigation · 2026Article
- Histone methyltransferase KMT2D promotes castration-resistant prostate cancer progression by reactivating AR through FOXA1.Oncogene · 2026Article
- KMT2D loss drives adeno-to-squamous transition and sensitizes TKI-resistant lung cancer to AURKA inhibition.Cell death and differentiation · 2026Article
- Paeoniflorin inhibits colorectal cancer stem cell properties via regulating LINC01711/KMT2D/KLF7 axis.Journal of gastrointestinal oncology · 2026Article
- PCGF1-mediated bivalent promoter remodeling enables NK cell immune evasion in non-small cell lung cancer.Cell death & disease · 2026Article
- Enhancer and metabolic rewiring by KMT2C-COMPASS or KMT2D-COMPASS family loss in cancer creates druggable vulnerabilities.Nature reviews. Cancer · 2026Review
- NRG4 suppresses breast cancer metastasis via ERBB4-YAP1-mediated down-regulation of MMPs.Genes & diseases · 2026Article
- Integration Analysis of Bayesian and Machine Learning for Heterogeneity, Biomarkers, and Optimal Combination Regimens of Pucotenlimab in Solid Tumors.Cancer medicine · 2026Article
- Amoeboid-mesenchymal transition and the proteolytic control of cancer invasion plasticity.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- KMT2C Loss Promotes NF2-Wildtype Meningioma Progression and Ferroptosis Sensitivity via Epigenetic Repression of Hippo Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- Histone lysine demethylases in breast cancer: molecular mechanisms, biological functions, and therapeutic intervention.Molecular cancer · 2025Review
- Multi-omics elucidation of KDM5C, KDM6A, and KMT2B roles in cancer epigenetic dysregulation and transcriptional reprogramming.Communications biology · 2025Article
- Epigenetic drivers of metalloproteinases and metastasis.Trends in cell biology · 2025Review
- Dasatinib Inhibits Basal B Breast Cancer Through ETS1-Mediated Extracellular Matrix Remodeling.Biomedicines · 2025Article
- Cancer-associated fibroblast-derived extracellular vesicles facilitate metastasis in hepatocellular carcinoma by delivering CTGF.Cellular oncology (Dordrecht, Netherlands) · 2025Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
KMT2C and KMT2D, encoding histone H3 lysine 4 methyltransferases, are among the most commonly mutated genes in triple-negative breast cancer (TNBC). However, how these mutations may shape epigenomic and transcriptomic landscapes to promote tumorigenesis is largely unknown. Here we describe that deletion of Kmt2c or Kmt2d in non-metastatic murine models of TNBC drives metastasis, especially to the brain. Global chromatin profiling and chromatin immunoprecipitation followed by sequencing revealed altered H3K4me1, H3K27ac and H3K27me3 chromatin marks in knockout cells and demonstrated enhanced binding of the H3K27me3 lysine demethylase KDM6A, which significantly correlated with gene expression. We identified Mmp3 as being commonly upregulated via epigenetic mechanisms in both knockout models. Consistent with these findings, samples from patients with KMT2C-mutant TNBC have higher MMP3 levels. Downregulation or pharmacological inhibition of KDM6A diminished Mmp3 upregulation induced by the loss of histone-lysine N-methyltransferase 2 (KMT2) and prevented brain metastasis similar to direct downregulation of Mmp3. Taken together, we identified the KDM6A-matrix metalloproteinase 3 axis as a key mediator of KMT2C/D loss-driven metastasis in TNBC.
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