ArticleCell death & disease2025
Histone lactylation promotes multidrug resistance in hepatocellular carcinoma by forming a positive feedback loop with PTEN.
Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed.
- Lactate Signal: Modulator of Cellular Energy Production and Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lactylation Remodels Tumorigenesis, Immune Microenvironment, and Therapeutic Response.Current issues in molecular biology · 2026Review
- Macrophage-reprogramming calcium alginate microspheres enhance exosome-mediated antigen cross-presentation to boost embolization-immunotherapy in hepatocellular carcinoma.Materials today. Bio · 2026Article
- The impact of microbial metabolites on host chromatin and epigenetic regulation.Nature metabolism · 2026Review
- Lactylation-driven therapeutic resistance in cancer: Mechanisms and therapeutic opportunities.Genes & diseases · 2026Review
- Clinical implications of lactylation modification in digestive system tumors (Review).Oncology letters · 2026Review
- Nuclear PD-L1: an emerging oncogenic driver and promising therapeutic target in cancer.Journal of biomedical science · 2026Review
- Lysine lactylation-mediated post-translational modification: Molecular mechanisms and therapeutic target exploration in tumour drug resistance.Clinical and translational medicine · 2026Review
- A tale of dual role: HECT‑type E3 ubiquitin ligase mechanisms in liver diseases (Review).International journal of molecular medicine · 2026Review
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Protein lactylation: a metabolic signal driving cancer therapy resistance.Cell death discovery · 2026Review
- Lactylation in tissue fibrosis: epigenetic mechanisms, metabolic crosstalk, and therapeutic opportunities.Journal of translational medicine · 2026Review
- Lactylation and acetylation: parallel paths, divergent deeds, and research dilemmas.Journal of translational medicine · 2026Review
- Histone lactylation-driven feedback loop modulates pyrimidine metabolism to promote oral carcinogenesis.Cell death & disease · 2026Article
- Review
- Multi-omics integration in deciphering non-small cell lung cancer drug resistance: current status, challenges, and future prospects.Hereditas · 2026Review
- Mechanisms of lactylation modification in hepatocellular carcinoma treatment resistance.Gastroenterology report · 2026Review
- Solasonine inhibits NSCLC malignant progression by regulating SLC7A11 ubiquitination degradation and inducing ferroptosis.Respiratory research · 2026Article
- Lactylation in cancer: molecular mechanisms and advances in clinical study.Molecular cancer · 2026Review
- Lactate Metabolism and Protein Lactylation in Diabetic Kidney Disease: A Narrative Review.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
FOLFOX (5-fluorouracil, oxaliplatin, folinic acid) is a standard treatment for hepatocellular carcinoma, but its efficacy is often limited by drug resistance, the underlying mechanisms of which remain unclear. In this study, oxaliplatin (OXA)- and 5-fluorouracil (5-Fu)-resistant hepatocellular carcinoma cell lines were established, and enhanced glycolytic activity was identified in resistant cells. Inhibiting glycolysis effectively suppressed the malignant behavior of both OXA- and 5-Fu-resistant cells. Mechanistically, active glycolysis induced elevated levels of lactylation, predominantly histone lactylation, with H3K14la playing a key role in regulating gene expression. The ubiquitin E3 ligase NEDD4 was identified as a downstream target of H3K14la. Furthermore, NEDD4, regulated by histone lactylation, interacted with PTEN to mediate its ubiquitination and subsequent degradation. The downregulation of PTEN formed a positive feedback loop, further driving the malignant progression of OXA- and 5-Fu-resistant cells. This study elucidates a shared mechanism underlying OXA and 5-Fu resistance in hepatocellular carcinoma and highlights a promising therapeutic target for overcoming clinical chemotherapy resistance.
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Registered trials
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 Socratic graph.