ArticleCell death and differentiation2025
KRAS mutation increases histone H3 lysine 9 lactylation (H3K9la) to promote colorectal cancer progression by facilitating cholesterol transporter GRAMD1A expression.
Article in Cell death and differentiation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed.
- Lactylation Remodels Tumorigenesis, Immune Microenvironment, and Therapeutic Response.Current issues in molecular biology · 2026Review
- USP48 functions as a suppressor of colorectal cancer via SELENBP1 stabilization.Translational oncology · 2026Article
- Review
- Causal relationship between immune factors and Guillain-Barré syndrome: A Mendelian randomization study.Medicine · 2026Article
- Glycolytic enolase 1-induced H4K12 lactylation activates quiescent breast cancer stem-like cells in triple-negative breast cancer.Signal transduction and targeted therapy · 2026Article
- Lactate as a Master Regulator of Immune Suppression: From Metabolic Waste to Epigenetic Checkpoint in Colorectal Cancer.International journal of molecular sciences · 2026Review
- LncRNA DLX6-AS1 promotes necroptosis through PI3K/AKT/mTOR signaling pathway in myocardial ischemia/reperfusion injury mice.Scientific reports · 2026Article
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- Beyond a Metabolite: Lactylation as a Pivotal Regulator of Colorectal Cancer Pathogenesis and Treatment Resistance.Journal of biochemical and molecular toxicology · 2026Review
- The impact of microbial metabolites on host chromatin and epigenetic regulation.Nature metabolism · 2026Review
- The crosstalk between RNA m6A modification and protein lactylation: emerging insights into tumor progression.Oncogene · 2026Review
- KRASScience advances · 2026Article
- S-propargyl-cysteine remodels the HCC microenvironment and potentiates anti-PD-1 therapy through CSE/HJournal of translational medicine · 2026Article
- Functional consistency and molecular evolution: a comprehensive characterization of primary endometrial cancer-associated fibroblasts during in vitro expansion.Journal of translational medicine · 2026Article
- Lactylation in Colorectal Cancer: Regulatory Networks, Functional Mechanisms, and Clinical Translational Potential.International journal of molecular sciences · 2026Review
- Methyltransferase MGMT upregulation drives metastasis by activating epithelial-mesenchymal transition in KRAS mutant colon cancer.Cell death & disease · 2026Article
- TRIPping anti-tumour immunity through lactylation.Nature metabolism · 2026Article
- SATB2 Mediates H3K9 Delactylation by Recruiting HDAC3 to Repress LCN2 and Inhibit Lung Tumor Growth and Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Protein lactylation: a metabolic signal driving cancer therapy resistance.Cell death discovery · 2026Review
- Protocadherin gamma subfamily A, 3 inhibits the proliferation and metastasis of lung adenocarcinoma by inhibiting transforming growth factor β signaling pathway.Respiratory research · 2026Article
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14 authors.
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Abstract
Histone lactylation is a novel epigenetic modification derived from lactate, but its role and mechanism in KRAS mutant colorectal cancer (CRC) progression remains to be fully elucidated. In this study, we first showed that mutant KRAS increased H3 lysine 9 lactylation (H3K9la) to promote CRC progression. We found that KRAS-mutant CRC tissues and cell lines exhibited higher lactylation and H3K9la levels compared to KRAS wild-type counterparts, driven by increased intracellular lactate. Elevated lactylation and H3K9la levels were associated with poor prognosis and advanced clinical stages. Inhibition of lactylation and H3K9la suppressed proliferation and migration of CRC cells. Mechanistically, mutant KRAS upregulated GRAMD1A expression by elevating H3K9la levels to increase chromatin accessibility. And increased GRAMD1A facilitated cholesterol metabolism to promote CRC growth and metastasis. Targeted inhibition of H3K9la or GRAMD1A reduced tumor growth in CRC patient-derived xenografts (PDX) models. Our study uncovered the critical role of H3K9la as a novel epigenetic modification in KRAS mutant CRC progression, suggesting H3K9la and its downstream gene GRAMD1A as promising targets for therapeutic intervention in KRAS mutant CRC and potential biomarkers for the prognosis of CRC patients.
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