ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Lactylation-Driven IGF2BP3-Mediated Serine Metabolism Reprogramming and RNA m6A-Modification Promotes Lenvatinib Resistance in HCC.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
What it found
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The trial behind it
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Who cites it
119 citing papers in PubMed.
- Unveiling the "Glycolysis-Lactate-Lactylation" Axis: A Novel Target in Ischemic Cerebrovascular Disease.Neuroscience bulletin · 2026Review
- IGF2BP3 promotes early angiogenesis in pulmonary fibrosis by stabilizing HIF-1α.Molecular and cellular biochemistry · 2026Article
- Review
- WTAP Transcriptional Suppression by KLF9 Drives Osteoclastogenesis via MAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- IGF2BP3 Overexpression Accelerates Osteoarthritis Progression by Promoting Glycolysis via mThe Kaohsiung journal of medical sciences · 2026Article
- Article
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- Targeting lactylation in hepatocellular carcinoma: Mechanistic insights and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Interplay between N6-methyladenosine RNA methylation and protein lactylation: a novel crosstalk linking metabolism and epigenetic regulation in human diseases.Journal of translational medicine · 2026Review
- RNF114-PACSIN3 signaling axis promotes hepatocellular carcinoma progression by enhancing GLUT1 membrane retention and glucose uptake.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Clinical implications of lactylation modification in digestive system tumors (Review).Oncology letters · 2026Review
- Lactylation-driven therapeutic resistance in cancer: Mechanisms and therapeutic opportunities.Genes & diseases · 2026Review
- IGF2BP3 promotes glycolysis of osteosarcoma stem cells by reading RNA m⁶A to stabilize ENO1 and promote malignant biological behavior of osteosarcoma.Cell biology and toxicology · 2026Article
- Bioinformatics mining and clinical validation of CD274 as a prognostic indicator in hepatocellular carcinoma.BMC cancer · 2026Article
- RNA methylation in cell death: mechanisms and clinical applications.Molecular cancer · 2026Review
- Targeting Cuproptosis and Ferroptosis via a ROS-Responsive Nanoplatform for Enhanced Synergistic Therapy Against Hepatocellular Carcinoma.Antioxidants (Basel, Switzerland) · 2026Article
- Prolonged S-adenosylmethionine exposure is associated with poorer treatment response and adverse outcomes in breast cancer: a retrospective cohort study.World journal of surgical oncology · 2026Article
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
59 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Acquired resistance remains a bottleneck for molecular-targeted therapy in advanced hepatocellular carcinoma (HCC). Metabolic adaptation and epigenetic remodeling are recognized as hallmarks of cancer that may contribute to acquired resistance. In various lenvatinib-resistant models, increased glycolysis leads to lactate accumulation and lysine lactylation of IGF2BP3. This lactylation is crucial for capturing PCK2 and NRF2 mRNAs, thereby enhancing their expression. This process reprograms serine metabolism and strengthens the antioxidant defense system. Additionally, altered serine metabolism increases the availability of methylated substrates, such as S-adenosylmethionine (SAM), for N6-methyladenosine (m6A) methylation of PCK2 and NRF2 mRNAs. The lactylated IGF2BP3-PCK2-SAM-m6A loop maintains elevated PCK2 and NRF2 levels, enhancing the antioxidant system and promoting lenvatinib resistance in HCC. Treatment with liposomes carrying siRNAs targeting IGF2BP3 or the glycolysis inhibitor 2-DG restored lenvatinib sensitivity in vivo. These findings highlight the connection between metabolic reprogramming and epigenetic regulation and suggest that targeting metabolic pathways may offer new strategies to overcome lenvatinib resistance in HCC.
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Registered trials
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