ArticleScientific reports2019
Mutant IDH1 confers resistance to energy stress in normal biliary cells through PFKP-induced aerobic glycolysis and AMPK activation.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Beyond the convergence of metabolic reprogramming in primary liver cancer: a comprehensive review on energy and lipids metabolism.Frontiers in cell and developmental biology · 2026Review
- PFKP in malignant tumors: bridging metabolic reprogramming, post-translational modifications, and the immunosuppressive microenvironment.Frontiers in cell and developmental biology · 2026Review
- Next-Generation Hydrogels for Biliary Organoid Engineering.Pharmaceuticals (Basel, Switzerland) · 2025Review
- SIRT7 drives energy metabolic shifts in endometriosis via interaction with TUFM and Rhoa/Rock/Akt pathway activation.Cellular and molecular life sciences : CMLS · 2025Article
- Phosphofructokinase-1 redefined: a metabolic hub orchestrating cancer hallmarks through multi-dimensional control networks.Journal of translational medicine · 2025Review
- Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer.Cells · 2025Review
- Article
- IDH Mutant Cholangiocarcinoma: Pathogenesis, Management, and Future Therapies.Current oncology (Toronto, Ont.) · 2025Review
- Applications of 3D models in cholangiocarcinoma.Frontiers in oncology · 2025Review
- Tumor organoids for primary liver cancers: A systematic review of current applications in diagnostics, disease modeling, and drug screening.JHEP reports : innovation in hepatology · 2024Article
- Proteomic analysis of serum extracellular vesicles from biliary tract infection patients to identify novel biomarkers.Scientific reports · 2024Article
- Opportunities and challenges of hepatocellular carcinoma organoids for targeted drugs sensitivity screening.Frontiers in oncology · 2022Review
- Metabolic adaptations in cancers expressing isocitrate dehydrogenase mutations.Cell reports. Medicine · 2021Review
- Organoids and Spheroids as Models for Studying Cholestatic Liver Injury and Cholangiocarcinoma.Hepatology (Baltimore, Md.) · 2021Review
- Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis.PloS one · 2021Article
- Application and research progress of organoids in cholangiocarcinoma and gallbladder carcinoma.American journal of cancer research · 2021Review
- Review
- Review
- Emerging Roles and Therapeutic Interventions of Aerobic Glycolysis in Glioma.OncoTargets and therapy · 2020Review
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Authors and funding
21 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolism is a critical regulator of cell fate determination. Recently, the significance of metabolic reprogramming in environmental adaptation during tumorigenesis has attracted much attention in cancer research. Recurrent mutations in the isocitrate dehydrogenase (IDH) 1 or 2 genes have been identified in several cancers, including intrahepatic cholangiocarcinoma (ICC). Mutant IDHs convert α-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG), which affects the activity of multiple α-KG-dependent dioxygenases including histone lysine demethylases. Although mutant IDH can be detected even in the early stages of neoplasia, how IDH mutations function as oncogenic drivers remains unclear. In this study, we aimed to address the biological effects of IDH1 mutation using intrahepatic biliary organoids (IBOs). We demonstrated that mutant IDH1 increased the formation of IBOs as well as accelerated glucose metabolism. Gene expression analysis and ChIP results revealed the upregulation of platelet isoform of phosphofructokinase-1 (PFKP), which is a rate-limiting glycolytic enzyme, through the alteration of histone modification. Knockdown of the Pfkp gene alleviated the mutant IDH1-induced increase in IBO formation. Notably, the high expression of PFKP was observed more frequently in patients with IDH-mutant ICC compared to in those with wild-type IDH (p < 0.01, 80.9% vs. 42.5%, respectively). Furthermore, IBOs expressing mutant IDH1 survived the suppression of ATP production caused by growth factor depletion and matrix detachment by retaining high ATP levels through 5' adenosine monophosphate-activated protein kinase (AMPK) activation. Our findings provide a systematic understanding as to how mutant IDH induces tumorigenic preconditioning by metabolic rewiring in intrahepatic cholangiocytes.
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