ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
PSMD14-Mediated LDHA Deubiquitination Upregulates ACLY Expression via H3K18 Lactylation to Promote Lipid Synthesis and Pancreatic Cancer Progression.
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 14 papers.
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Who cites it
14 citing papers in PubMed.
- Lactylation Remodels Tumorigenesis, Immune Microenvironment, and Therapeutic Response.Current issues in molecular biology · 2026Review
- Lactate-induced epithelial-mesenchymal transition: a metabolic nexus in pancreatic cancer metastasis.Translational cancer research · 2026Review
- Metabolic Reprogramming in Glioblastoma Stem Cells Promotes Radiation Resistance Through a H3K18la/USP30/MBOAT2 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Histone lactylation: a novel epigenetic bridge linking cellular metabolism to benign and malignant gynecological diseases.Clinical epigenetics · 2026Review
- Protein modification systems as cancer biomarkers and therapeutic targets.Precision clinical medicine · 2026Review
- Targeting PSMD14 enhances immunotherapy efficacy by promoting PD-L1 degradation and reshaping the tumor microenvironment in breast cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Dapagliflozin May Attenuate Podocyte Injury in Diabetic Kidney Disease through Inhibition of Lactate-Mediated H4K12 Lactylation.Kidney & blood pressure research · 2026Article
- Association of Serum Lactate Dehydrogenase With Sepsis-Associated Acute Kidney Injury: A Large-Scale Analysis Based on the MIMIC-IV Database.Emergency medicine international · 2026Article
- PSMD14 as a translational target in cancer and beyond: from deubiquitination mechanisms to drug resistance and precision therapy.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- The symbiotic axis between the acidic tumor microenvironment and cancer stem cells: a driver of malignancy and therapeutic resistance.Frontiers in oncology · 2026Review
- The regulatory roles of dysregulated lactate dehydrogenase A in anti-tumor immunity within immune cells.Frontiers in immunology · 2026Review
- When metabolic enzymes meet lactylation: a bidirectional dialogue in health and disease.Frontiers in cell and developmental biology · 2026Review
- Targeting Lactylation for Cancer: Mechanisms, Effects, and Therapeutic Prospects.International journal of molecular sciences · 2025Review
- PSMD14-Mediated LDHA Deubiquitination Upregulates ACLY Expression via H3K18 Lactylation to Promote Lipid Synthesis and Pancreatic Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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11 authors.
Funding
Abstract
Aberrant lipid metabolism is intimately linked to tumor progression. As a pivotal post-translational modification, ubiquitination regulates diverse oncogenic processes. However, the interplay between ubiquitination and lipid metabolic dysregulation in pancreatic cancer (PC), along with its underlying molecular mechanisms, remains poorly understood. Here, it is demonstrated that glycolytic enzyme lactate dehydrogenase A (LDHA) potentiates lipid biosynthesis under the regulation of deubiquitinases. Specifically, PSMD14 directly binds and stabilizes LDHA through its deubiquitinase activity, resulting in intracellular lactate accumulation. Elevated lactate levels enhance histone lactylation marks, which transcriptionally activate ATP citrate lyase (ACLY) to promote malignant progression via fatty acid synthesis pathway activation. This study reveals a previously unrecognized role of PSMD14-derived lactate in mediating histone lactylation-coupled lipid deposition and tumor progression. Therapeutic co-targeting of PSMD14 and glycolytic lactylation significantly suppresses tumor growth in patient-derived xenograft models, suggesting a promising combinatorial strategy for pancreatic cancer treatment.
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