ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
Lactylation Enhances the Activity of Lactate Dehydrogenase A and Promotes the Chemoresistance to Cisplatin Through Facilitating DNA Nonhomologous End Junction in Lung Adenocarcinoma.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The trial behind it
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Who cites it
20 citing papers in PubMed.
- Research progress on lactate metabolism in lung cancer: Tumorigenesis, drug resistance and clinical translation (Review).Oncology reports · 2026Review
- HNRNPU K181 Lactylation Drives Cervical Cancer Growth by Upregulating PHGDH and Reprogramming Serine Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Lysine lactylation-mediated post-translational modification: Molecular mechanisms and therapeutic target exploration in tumour drug resistance.Clinical and translational medicine · 2026Review
- Lactylation in cardiac repair: Nexus and therapeutic opportunity.Journal of molecular and cellular cardiology plus · 2026Review
- Lactylation in Colorectal Cancer: Regulatory Networks, Functional Mechanisms, and Clinical Translational Potential.International journal of molecular sciences · 2026Review
- POU2F1 Promotes Chemoresistance in Colorectal Cancer Cells via Attenuates the MDR2 Degradation Mediated by PPP1R11 Lactylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Protein lactylation: a metabolic signal driving cancer therapy resistance.Cell death discovery · 2026Review
- Processes and therapeutic perspectives of acylation modifications of lysine and cysteine in tumors.Cell communication and signaling : CCS · 2026Review
- Research progress on protein lactylation in female reproductive disease: molecular mechanisms, functions, and therapeutic implications.Frontiers in pharmacology · 2026Review
- The role of protein lactylation in skin diseases: from molecular mechanisms to potential therapeutics.Frontiers in immunology · 2026Review
- The regulatory roles of dysregulated lactate dehydrogenase A in anti-tumor immunity within immune cells.Frontiers in immunology · 2026Review
- Lactylation Enhances the Activity of Lactate Dehydrogenase A and Promotes the Chemoresistance to Cisplatin Through Facilitating DNA Nonhomologous End Junction in Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ANP32A interacts with LDHA to modulate glycolysis and ferroptosis in hepatocellular carcinoma.Frontiers in oncology · 2026Article
- When metabolic enzymes meet lactylation: a bidirectional dialogue in health and disease.Frontiers in cell and developmental biology · 2026Review
- Post-translational protein lactylation modification in lung cancer: an emerging targeted therapeutic strategy.Frontiers in immunology · 2026Review
- Mechanistic role of glycolytic pathways in the tumor microenvironment in driving chemoresistance.Frontiers in cell and developmental biology · 2026Review
- Advances in plasma metabolomics detection technology and its clinical applications in lung cancer and other malignancies.Holistic integrative oncology. · 2026Review
- Lactate and lactylation in sepsis: regulation of immune-metabolic crosstalk and organ injury.Frontiers in immunology · 2026Review
- GUDCA drives colorectal cancer progression via ALKBH5-mediated m6A modification of ENO1 and glycolytic reprogramming.Frontiers in pharmacology · 2026Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Lactylation is a novel post-translational modification closely related to the glycolytic process, but the regulatory mechanisms between lactylation and glycolysis are far from being elucidated. Lactate dehydrogenase A (LDHA) catalyzes the formation of lactate, which provides the modifying group for protein lactylation. However, whether lactylation occurs on LDHA itself remains unknown. Here, it is found that lactylation promotes the enzymatic activity of LDHA in lung adenocarcinoma (LUAD), which in turn enhances the overall level of cellular lactylation through a positive feedback loop. Screening identified Lys81 and Lys318 as key LDHA lactylation sites, with alanyl-tRNA synthetase 1 (AARS1) serving as the mediating lactyltransferase. Mass spectrometry reveals that numerous proteins involved in DNA nonhomologous end junction (NHEJ), including FEN1, XRCC5, and XRCC6 might be regulated by lactylation. Delactylation of these proteins significantly hinders the formation of FEN1-RAD1-RAD9A-HUS1 complex, thereby leading to dysfunction of NHEJ and increasing the sensitivity of cancer cells to cisplatin. In summary, this work identifies LDHA lactylation as a critical mechanism for accelerating the progression of LUAD and reveals how this lactylation influenced cisplatin sensitivity of LUAD cells, which deepen the understanding of lactylation-mediated tumor progression and provide a potential new anticancer strategy.
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