ArticleJournal of translational medicine2023
Warburg effect enhanced by AKR1B10 promotes acquired resistance to pemetrexed in lung cancer-derived brain metastasis.
Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 77 citations in OpenAlex.
- Lactylation in gastric cancer: From mechanisms to clinical applications (Review).Molecular medicine reports · 2026Review
- Genes, fuel, and fate in lung cancer.Biochemical Society transactions · 2026Review
- Research progress on lactate metabolism in lung cancer: Tumorigenesis, drug resistance and clinical translation (Review).Oncology reports · 2026Review
- Lung Cancer Brain Metastasis: Brain Microenvironmental Adaptation, Therapeutic Resistance and Translational Strategies.Cancer science · 2026Review
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Epigenetics in lung cancer precision medicine: from bench to bedside-a narrative review.Translational lung cancer research · 2026Review
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- IER3 as an RFX5 transcriptional co-activator promotes hepatocellular carcinoma progression via AKR1B10-mediated p53 transcriptional regulation.Discover oncology · 2026Article
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Immune cross talk and therapeutic advances in lactate metabolism in the tumor microenvironment (Review).Experimental and therapeutic medicine · 2026Review
- Coordinated Multicellular Immune Programs and Drug Targets Revealed by Single-Cell Analysis in Driver-Mutated NSCLC.International journal of molecular sciences · 2026Article
- DNA hypermethylation drives BVES-mediated autophagy to promote cisplatin resistance in lung adenocarcinoma.Journal of bioenergetics and biomembranes · 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
- LDHA-Mediated H3K18 Lactylation Promotes the Glycolysis in Non-Small Cell Lung Cancer Through Targeting PTEN.Biochemical genetics · 2026Article
- The controversial role of metabolic reprogramming in anti-tumor therapy resistance.Discover oncology · 2026Review
- Lactylation as a metabolic-epigenetic switch in cancer: dual roles in cell death resistance and therapeutic vulnerability.Cell death & disease · 2026Review
- Review
- AKR1B10 reprograms neutrophils by histone lactylation to foster immune evasion in KRASJournal of experimental & clinical cancer research : CR · 2026Article
- The evolving landscape of brain metastasis: volume II.Trends in cancer · 2026Review
- [Research Progress on Glycolytic Reprogramming and Lactylation Crosstalk in Tumors].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundResistance to pemetrexed (PEM), a rare chemotherapeutic agent that can efficiently cross the blood-brain barrier, limits the therapeutic efficacy for patients with lung cancer brain metastasis (BM). Aldo-keto reductase family 1 B10 (AKR1B10) was recently found to be elevated in lung cancer BM. The link between AKR1B10 and BM-acquired PEM is unknown.
methodsPEM drug-sensitivity was assessed in the preclinical BM model of PC9 lung adenocarcinoma cells and the BM cells with or without AKR1B10 interference in vitro and in vivo. Metabolic reprogramming of BM attributed to AKR1B10 was identified by chromatography-mass spectrometry (GC-MS) metabolomics, and the mechanism of how AKR1B10 mediates PEM chemoresistance via a way of modified metabolism was revealed by RNA sequencing as well as further molecular biology experimental approaches.
resultsThe lung cancer brain metastatic subpopulation cells (PC9-BrM3) exhibited significant resistance to PEM and silencing AKR1B10 in PC9-BrM3 increased the PEM sensitivity in vitro and in vivo. Metabolic profiling revealed that AKR1B10 prominently facilitated the Warburg metabolism characterized by the overproduction of lactate. Glycolysis regulated by AKR1B10 is vital for the resistance to PEM. In mechanism, AKR1B10 promoted glycolysis by regulating the expression of lactate dehydrogenase (LDHA) and the increased lactate, acts as a precursor that stimulates histone lactylation (H4K12la), activated the transcription of CCNB1 and accelerated the DNA replication and cell cycle.
conclusionsOur finding demonstrates that AKR1B10/glycolysis/H4K12la/CCNB1 promotes acquired PEM chemoresistance in lung cancer BM, providing novel strategies to sensitize PEM response in the treatment of lung cancer patients suffering from BM.
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