ArticleCancer gene therapy2022
γ-Glutamylcyclotransferase, a novel regulator of HIF-1α expression, triggers aerobic glycolysis.
Article in Cancer gene therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- Knowledge mapping and current trends of Warburg effect in the field of cancer.Frontiers in oncology · 2023Pooled it
- Mechanism of Bao Jing Tablets in Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Insights from Multi-Omics and Network Pharmacology.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Comprehensive analysis of GGCT genes in u's triangle Brassica species: insights into abiotic stress responses and potential association of BnaGGCT11/26 with seed weight.BMC plant biology · 2025Article
- GGCT participates in the malignant process of hepatocellular cancer cells by regulating the PTEN/PI3K/AKT pathway through binding to EZH2.Discover oncology · 2025Article
- Computational-experimental strategy identifies Co-upregulated biomarkers linking coronary heart disease and type 2 diabetes pathogenesis.Frontiers in genetics · 2025Article
- Identified γ-glutamyl cyclotransferase (GGCT) as a novel regulator in the progression and immunotherapy of pancreatic ductal adenocarcinoma through multi-omics analysis and experiments.Journal of cancer research and clinical oncology · 2024Article
- Identification of c-Met as a novel target of γ-glutamylcyclotransferase.Scientific reports · 2023Article
- MiR-205-5p/GGCT Attenuates Growth and Metastasis of Papillary Thyroid Cancer by Regulating CD44.Endocrinology · 2022Article
- Oxidative and Antioxidative Status Expressed as OSI Index and GSH/GSSG Ratio in Children with Bone Tumors after Anticancer Therapy Completion.Journal of clinical medicine · 2022Article
- Effect of Regorafenib on P2X7 Receptor Expression and Different Oncogenic Signaling Pathways in a Human Breast Cancer Cell Line: A Potential of New Insight of the Antitumor Effects of Regorafenib.Current issues in molecular biology · 2021Article
- Quercetin Antagonizes Glucose Fluctuation Induced Renal Injury by Inhibiting Aerobic Glycolysis via HIF-1α/miR-210/ISCU/FeS Pathway.Frontiers in medicine · 2021Article
- Desert Hedgehog Down-regulation Mediates Inhibition of Proliferation by γ-Glutamylcyclotransferase Knockdown in Murine Glioblastoma Stem Cells.Cancer genomics & proteomicsArticle
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Metabolic reprogramming leading to aerobic glycolysis, termed the "Warburg effect," is a critical property of cancer cells. However, the precise mechanisms underlying this phenomenon are not fully understood. A growing body of evidence indicates that γ-glutamylcyclotransferase (GGCT), an enzyme involved in glutathione homeostasis that is highly expressed in many types of cancer, represents a promising therapeutic target. In this study, we identified GGCT as a novel regulator of hypoxia-inducible factor-1α (HIF-1α), a transcription factor that plays a role in hypoxia adaptation promoting aerobic glycolysis. In multiple human cancer cell lines, depletion of GGCT downregulated HIF-1α at the mRNA and protein levels. Conversely, in NIH3T3 mouse fibroblasts, overexpression of GGCT upregulated HIF-1α under normoxia. Moreover, depletion of GGCT downregulated HIF-1α downstream target genes involved in glycolysis, whereas overexpression of GGCT upregulated those genes. Metabolomic analysis revealed that modulation of GGCT expression induced a metabolic switch from the citric acid cycle to glycolysis under normoxia. In addition, we found that GGCT regulates expression of HIF-1α protein via the AMPK-mTORC1-4E-BP1 pathway in PC3 cells. Thus GGCT regulates the expression of HIF-1α in cancer cells, causing a switch to glycolysis.
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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 OpenQuestion graph.