ArticleThe EMBO journal2023
IDH2 stabilizes HIF-1α-induced metabolic reprogramming and promotes chemoresistance in urothelial cancer.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 74 citations in OpenAlex.
- Multimodal AI and single-cell transcriptomics integrate to construct a histopathological prognostic model for bladder cancer, revealing the RTN3-glycolysis axis in chemoresistance.Experimental hematology & oncology · 2026Article
- Single-cell immune atlas of mouse testes unveils metabolic reprogramming of FOLR2 + macrophages in orchestrating testicular immunity during aging.GeroScience · 2026Article
- Metal-organic framework nanoparticles induced non-apoptotic cell death: Construction, mechanisms, and cancer therapy.Materials today. Bio · 2026Review
- Mitochondrial superoxide sustains a senescence-like phenotype in PARP- inhibited ovarian cancer cells by stabilizing HIF1α.Redox biology · 2026Article
- T2* mapping in magnetic resonance imaging for stratifying the hypoxic microenvironment in pancreatic ductal adenocarcinoma: a preliminary study.Quantitative imaging in medicine and surgery · 2026Article
- Cigarette Smoking-RegulatedEnvironment & health (Washington, D.C.) · 2026Article
- A machine learning-based epigenetic signature reveals YTHDC1 stabilizes POU5F1 to oppose tumor progression.Journal of translational medicine · 2026Article
- The controversial role of metabolic reprogramming in anti-tumor therapy resistance.Discover oncology · 2026Review
- Citric Acid Cycle Genes and Nutrigenetics.International journal of molecular sciences · 2026Review
- Ferroptosis-autophagy crosstalk in bladder cancer: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- USP10 promotes cell proliferation and gemcitabine resistance in pancreatic cancer by the regulation of IGF2BP3-STEAP3.Oncogene · 2026Article
- RHOJ derived peptide promotes chemosensitivity by inhibiting glutamine metabolism in gastric cancer.Journal of translational medicine · 2026Article
- Aerobic glycolysis in bladder cancer: research advances and targeted therapy potential.Frontiers in oncology · 2026Review
- Mechanisms of resistance to antibody-drug conjugates in bladder cancer.Frontiers in pharmacology · 2026Review
- Enhancement of gemcitabine toxicity and specificity through PI3K/Akt/Nrf2 pathway inhibition in pancreatic cancer.Frontiers in pharmacology · 2026Article
- An exploration of GuaLouQuMaiWan related novel prognostic model and search for potential compound pachymic acid in bladder cancer.Frontiers in oncology · 2026Article
- INHBA promotes chemoresistance in pancreatic cancer by enhancing CTPS1 stability and mediating pyrimidine metabolism.Cancer cell international · 2025Article
- Association of urinary tract infection and low albumin/globulin ratio with chemoresistance to gemcitabine-cisplatin in advanced urothelial carcinoma.The Canadian journal of urology · 2025Article
- The deubiquitylase OTUB1 drives gemcitabine resistance in pancreatic cancer by enhancing pyrimidine metabolism through modulating DHODH mRNA stability.Cell death & disease · 2025Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug resistance contributes to poor therapeutic response in urothelial carcinoma (UC). Metabolomic analysis suggested metabolic reprogramming in gemcitabine-resistant urothelial carcinoma cells, whereby increased aerobic glycolysis and metabolic stimulation of the pentose phosphate pathway (PPP) promoted pyrimidine biosynthesis to increase the production of the gemcitabine competitor deoxycytidine triphosphate (dCTP) that diminishes its therapeutic effect. Furthermore, we observed that gain-of-function of isocitrate dehydrogenase 2 (IDH2) induced reductive glutamine metabolism to stabilize Hif-1α expression and consequently stimulate aerobic glycolysis and PPP bypass in gemcitabine-resistant UC cells. Interestingly, IDH2-mediated metabolic reprogramming also caused cross resistance to CDDP, by elevating the antioxidant defense via increased NADPH and glutathione production. Downregulation or pharmacological suppression of IDH2 restored chemosensitivity. Since the expression of key metabolic enzymes, such as TIGAR, TKT, and CTPS1, were affected by IDH2-mediated metabolic reprogramming and related to poor prognosis in patients, IDH2 might become a new therapeutic target for restoring chemosensitivity in chemo-resistant urothelial carcinoma.
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