ArticleNature communications2017
Nur77 suppresses hepatocellular carcinoma via switching glucose metabolism toward gluconeogenesis through attenuating phosphoenolpyruvate carboxykinase sumoylation.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 2 of them syntheses that pooled it.
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Who cites it
86 citing papers in PubMed, 2 syntheses or guidelines pooled it, 135 citations in OpenAlex.
- Association of metformin use and cancer incidence: a systematic review and meta-analysis.Journal of the National Cancer Institute · 2024 · on this mapPooled it
- NR4A Family Genes: A Review of Comprehensive Prognostic and Gene Expression Profile Analysis in Breast Cancer.Frontiers in oncology · 2022Pooled it
- Nur77 agonism invigorates Natural Killer cell immunity against hepatocellular carcinoma.Nature communications · 2026Article
- SUMOylation-stabilized G6PD orchestrates metabolic rewiring for oxidative stress survival and chemoresistance in HCC via a PKCδ-phosphorylation trigger.Cell death and differentiation · 2026Article
- TRIM26-mediated NKRF degradation drives Osimertinib resistance through SNRPD2-dependent stress granule formation in lung adenocarcinoma.Cell death & disease · 2026Article
- <p>KMO downregulation promotes hepatocellular carcinoma growth via 3‑HAA‑mediated mitochondrial mass and function imbalances</p>.International journal of oncology · 2026Article
- A Unique Intercellular Feedforward Loop From HK1 to TGF-β1 Promotes the Progression of Hepatocellular Carcinoma.Journal of extracellular vesicles · 2026Article
- Rottlerin triggers dual degradation of SLC7A11 and GPX4 to drive ferroptosis and chemosensitization in hepatocellular carcinoma.Cell death discovery · 2026Article
- The landscape of gut microbiota in hepatocarcinogenesis: a comprehensive review of pathogenesis and therapeutic interventions.International journal of surgery (London, England) · 2026Review
- Nurr1 deficiency orchestrates a coupled liver-gut pathological axis revealed by multi-omics and deep-learning histopathology.Frontiers in immunology · 2026Article
- Disruption of heme homeostasis by nuclear receptor Nur77 induces pyroptosis through granzyme B-dependent GSDMC cleavage.Signal transduction and targeted therapy · 2025Article
- The nuclear receptor NR6A1 plays an oncogenic role through reprogramming glycolysis in tumors.Biological research · 2025Article
- ERK1-mediated GLYCTK2 phosphorylation promotes fructolysis to sustain glioblastoma survival under glucose deprivation.Cell death discovery · 2025Article
- c-Myc-dependent LAMP3 regulates the proliferation, metastasis and metabolic reprogramming of tongue squamous cell carcinoma.Scientific reports · 2025Article
- NR4A1 Acts as a Novel Regulator of Platelet Activation and Thrombus Formation.Circulation research · 2025Article
- NR4A1 suppresses breast cancer growth by repressing c-Fos-mediated lipid and redox dyshomeostasis.Experimental & molecular medicine · 2025Article
- Controversy and multiple roles of the solitary nucleus receptor Nur77 in disease and physiology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Article
- PDHX acetylation facilitates tumor progression by disrupting PDC assembly and activating lactylation-mediated gene expression.Protein & cell · 2025Article
- The impact of metabolic reprogramming in hepatocellular carcinoma on T cell.Frontiers in immunology · 2025Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gluconeogenesis, an essential metabolic process for hepatocytes, is downregulated in hepatocellular carcinoma (HCC). Here we show that the nuclear receptor Nur77 is a tumour suppressor for HCC that regulates gluconeogenesis. Low Nur77 expression in clinical HCC samples correlates with poor prognosis, and a Nur77 deficiency in mice promotes HCC development. Nur77 interacts with phosphoenolpyruvate carboxykinase (PEPCK1), the rate-limiting enzyme in gluconeogenesis, to increase gluconeogenesis and suppress glycolysis, resulting in ATP depletion and cell growth arrest. However, PEPCK1 becomes labile after sumoylation and is degraded via ubiquitination, which is augmented by the p300 acetylation of ubiquitin-conjugating enzyme 9 (Ubc9). Although Nur77 attenuates sumoylation and stabilizes PEPCK1 via impairing p300 activity and preventing the Ubc9-PEPCK1 interaction, Nur77 is silenced in HCC samples due to Snail-mediated DNA methylation of the Nur77 promoter. Our study reveals a unique mechanism to suppress HCC by switching from glycolysis to gluconeogenesis through Nur77 antagonism of PEPCK1 degradation.
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