ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
High Sugar Induced RCC2 Lactylation Drives Breast Cancer Tumorigenicity Through Upregulating MAD2L1.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- HNRNPU K181 Lactylation Drives Cervical Cancer Growth by Upregulating PHGDH and Reprogramming Serine Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Lactylation-driven therapeutic resistance in cancer: Mechanisms and therapeutic opportunities.Genes & diseases · 2026Review
- LINC01614 favors breast cancer progression through the regulation of miR-217/FN1 and mediation in PI3K/AKT signal pathway.Translational cancer research · 2026Article
- KAT2A-IGF2BP1-CXCL2 axis in the high lactate tumor microenvironment facilitates resistance to anti-PD-1 therapy in lung adenocarcinoma by recruiting myeloid-derived suppressor cells.Cell death & disease · 2026Article
- Metabolic Signaling Meets Epigenetic Regulation: How Protein Lactylation Remodels the Tumor Immune Microenvironment in Gastric Cancer.Current issues in molecular biology · 2026Review
- Lactate metabolism and lactylation in female reproductive diseases: From metabolic rewiring to biomarkers and translational therapeutics.Clinical and translational medicine · 2026Review
- Lactylation enzymes in cancer: Mechanisms and novel therapeutic approaches (Review).Oncology letters · 2026Review
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Inhibition of Histone Lactylation by Dichloromethane Extract From Patrinia scabiosaefolia Fisch on Acute Myeloid Leukemia Cells.Chemistry & biodiversity · 2026Article
- Epigenetic regulation in a high-sugar environment (Review).International journal of molecular medicine · 2026Review
- AARS1-mediated AKR1B10 lactylation stabilizes an aerobic glycolysis-positive feedback loop to drive lenvatinib resistance in hepatocellular carcinoma.Clinical and translational medicine · 2026Article
- Integrated Proteogenomic Characterization Identifies Breast Cancer Immune Subgroups and Subtype-Specific Therapeutic Strategies.Research (Washington, D.C.) · 2026Article
- Lactylation Modification: From Basic Biological Process to Clinical Cardiovascular Diseases.Research (Washington, D.C.) · 2026Review
- Lactylation-driven KRT19 promotes non-small cell lung cancer progression by suppressing cellular senescence.Journal of experimental & clinical cancer research : CR · 2025Article
- Targeting Lactylation for Cancer: Mechanisms, Effects, and Therapeutic Prospects.International journal of molecular sciences · 2025Review
- SERBP1: A Multifunctional RNA-Binding Protein Linking Gene Expression, Cellular Metabolism, and Diseases.Cells · 2025Review
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12 authors.
Funding
Abstract
Lactylation is a novel post-translational modification mediated by lactate, widely present in the lysine residues of both histone and non-histone proteins. However, the specific regulatory mechanisms and downstream target proteins remain unclear. Herein, it is demonstrated that the RCC2 protein may serve as a critical link between material metabolism and cell division, promoting the rapid proliferation of breast cancer under high glucose conditions. Mechanistically, the activation of glycolysis leads to an increase in lactate. Then, acyltransferase KAT2A mediates RCC2 lactylation at K124, which assists RCC2 in recruiting free SERBP1, thereby stabilizing MAD2L1 mRNA. The lactylation of RCC2 mediates the activation of the cellular MAD2L1 signaling pathway and contributes to the progression of breast cancer. A small molecule inhibitor slows down cell proliferation by binding to the RCC2 active pocket and specifically blocking RCC2 lactylation. The findings elucidate the mechanism behind the upregulation of MAD2L1 in murine tumors associated with a high-sugar diet as reported in prior study and suggest a novel therapeutic strategy of targeting RCC2 lactylation to restrict the rapid proliferation of breast cancer cell in a high-lactate microenvironment.
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