ArticleNature communications2025
Cholangiocarcinoma PDHA1 succinylation suppresses macrophage antigen presentation via alpha-ketoglutaric acid accumulation.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- DONSON links tumor-cell survival to MIF-associated macrophage remodeling in small cell lung cancer.Apoptosis : an international journal on programmed cell death · 2026Article
- α-KG conformationally stabilizes nuclear GLUD1-SNAIL complex to fuel trans-endothelial migration in metastasis.Nature communications · 2026Article
- DLST Succinylation-Mediated Mitochondrial Metabolic Remodeling and Cuproptosis Resistance Promote Malignant Progression of Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- A multi-omics analysis of a succinylation-associated gene-expression signature in clear cell renal cell carcinoma: prognostic significance and the immune-metabolic microenvironment.Genes & genomics · 2026Article
- Review
- A succinylation-based classifier predicts chemotherapy response in prostate cancer and reveals KAT2A as a therapeutic target.Clinical and translational medicine · 2026Article
- Targeting CD3L1-NRP2 disarms myeloid-driven tumor immune evasion.EMBO molecular medicine · 2026Article
- Multi-omics mapping identifies a C/EBPβ-S100a4⁺ macrophage axis as a therapeutic target in acute spinal cord injury.Journal of translational medicine · 2026Article
- PRMT1-mediated asymmetric dimethylation of arginine residue 602 in DDX1 promotes cholangiocarcinoma progression.Clinical and molecular hepatology · 2026Article
- Succinylation: A novel regulatory axis in cholelithiasis-insights from lysine acetyltransferase 2A/adenosine monophosphate-activated protein kinase signaling.World journal of gastroenterology · 2026Article
- Cuproptosis-associated PDHA1 promotes sarcoma progression and immunotherapy responsiveness via the E2F1-PD-L1 axis: a multi-omics and clinical validation study.NPJ precision oncology · 2026Article
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- Alpha-ketoglutarate Potentiates IL-1β Production and Suppressive Mechanisms of Myeloid-Derived Suppressor Cells by Altering Redox Metabolism and Inducing Autophagy.International journal of biological sciences · 2026Article
- PDHA1 Hyperactivation Orchestrates Metabolic Reprogramming Promoting Endothelial Senescence.Research (Washington, D.C.) · 2026Article
- Tenuigenin regulates succinylation via SIRT5 for suppressing the tumorigenicity of hepatocellular carcinoma cells.Frontiers in pharmacology · 2026Article
- Succinylation in cancer immunotherapy: mechanisms, biomarkers, and therapeutic implications.Frontiers in immunology · 2026Review
- Targeting cuproptosis for treatment and prognostic assessment in endometrial cancer.Cancer cell international · 2025Review
Corrections and comments
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Authors and funding
24 authors.
Funding
Abstract
Gemcitabine combined with cisplatin is the first-line chemotherapy for advanced cholangiocarcinoma, but drug resistance remains a challenge, leading to unsatisfactory therapeutic effect. Here, we elucidate the possibility of chemotherapy regimens sensitized by inhibiting succinylation in patients with cholangiocarcinoma from the perspective of post-translational modification. Our omics analysis reveals that succinylation of PDHA1 lysine 83, a key enzyme in the tricarboxylic acid cycle, alters PDH enzyme activity, modulates metabolic flux, and leads to alpha-ketoglutaric acid accumulation in the tumor microenvironment. This process activates the OXGR1 receptor on macrophages, triggering MAPK signaling and inhibiting MHC-II antigen presentation, which promotes immune escape and tumor progression. Moreover, we show that inhibiting PDHA1 succinylation with CPI-613 enhances the efficacy of gemcitabine and cisplatin. Targeting PDHA1 succinylation may be a promising strategy to improve treatment outcomes in cholangiocarcinoma and warrants further clinical exploration.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.