ArticleClinical and translational medicine2022
Dysregulated glucuronic acid metabolism exacerbates hepatocellular carcinoma progression and metastasis through the TGFβ signalling pathway.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Multiancestry Transcriptome-Wide Association Study Identifies Candidate Genes Associated with Hepatoblastoma.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025Pooled it
- Targeting UXS1-Dependent Glucuronate Detoxification Potentiates Metformin's Anti-Tumor Efficacy in Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- UXS1 Knockdown Suppresses Cell Proliferation and Invasion in Hepatocellular Carcinoma by Inducing Ferroptosis via SLC7A11/GPX4 Pathway.Current medical science · 2026Article
- Enzyme-AssistedInternational journal of molecular sciences · 2026Article
- Metabolic characteristics in hepatocellular carcinoma: amino acid metabolic reprogramming.Molecular cancer · 2026Review
- ACPA prevents lung fibroblast-to-CAF transformation by reprogramming the tumor microenvironment through NSCLC-derived exosomes.Scientific reports · 2025Article
- A Synthetic Lectin for Glucuronate.ACS central science · 2025Article
- Phosphoglycerate dehydrogenase stabilizes protein kinase C delta type mRNA to promote hepatocellular carcinoma progression.Signal transduction and targeted therapy · 2025Article
- Pan-cancer analysis of UDP-glucose 6-dehydrogenase in human tumors and its function in hepatocellular carcinoma.World journal of gastrointestinal oncology · 2025Article
- Downregulation of UDP-glucose 6-dehydrogenase predicts adverse outcomes in patients with colorectal cancer and promotes tumorigenesis.Scientific reports · 2025Article
- Elevated UDP-glucuronic acid levels mend drug resistance and stress responses via a protease and a transporter inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- E3 ligase HERC5-catalyzed UGDH isgylation promotes SNAI1-mediated tumor metastasis and cisplatin resistance in oral squamous cell carcinoma.Biology direct · 2025Article
- Inverse-Vaccines for Rheumatoid Arthritis Re-establish Metabolic and Immunological Homeostasis in Joint Tissues.Advanced healthcare materials · 2025Article
- Nontargeted metabolomics uncovering metabolite signatures in glioblastoma: a preliminary study on candidate biomarker discovery for IDH subtyping and survival prediction.Frontiers in oncology · 2025Article
- Serum metabolic profiling of patients with diabetic kidney disease based on gas chromatography-mass spectrometry.Frontiers in molecular biosciences · 2025Article
- Vitamin D alleviates HFD-induced hepatic fibrosis by inhibiting DNMT1 to affect the TGFβ1/Smad3 pathway.iScience · 2024Article
- Salivary Metabolic Pathway Alterations in Brazilian E-Cigarette Users.International journal of molecular sciences · 2024Article
- Signaling metabolite succinylacetone activates HIF-1α and promotes angiogenesis in GSTZ1-deficient hepatocellular carcinoma.JCI insight · 2023Article
- Article
- Dysregulated glucuronic acid metabolism exacerbates hepatocellular carcinoma progression and metastasis through the TGFβ signalling pathway.Clinical and translational medicine · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGlucuronic acid metabolism participates in cellular detoxification, extracellular matrix remodeling and cell adhesion and migration. Here, we aimed to explore the crosstalk between dysregulated glucuronic acid metabolism and crucial metastatic signalling in glutathione S-transferase zeta 1 (GSTZ1)-deficient hepatocellular carcinoma (HCC).
methodsTranswell, HCC xenograft and Gstz1
resultsGSTZ1 was universally silenced in both human and murine HCC cells, and its deficiency contributed to HCC metastasis in vitro and in vivo. UDP-glucose 6-dehydrogenase (UGDH)-mediated UDP-glucuronic acid (UDP-GlcUA) accumulation promoted hepatoma cell migration upon GSTZ1 loss. UDP-GlcUA stabilized TGFβR1 mRNA by enhancing its binding to polypyrimidine tract binding protein 3, contributing to the activation of TGFβ/Smad signalling. UGDH or TGFβR1 blockade impaired HCC metastasis. In addition, UGDH up-regulation and UDP-GlcUA accumulation correlated with increased metastatic potential and decreased patient survival in GSTZ1-deficient HCC.
conclusionsGSTZ1 deficiency and subsequent up-regulation of the glucuronic acid metabolic pathway promotes HCC metastasis by increasing the stability of TGFβR1 mRNA and activating TGFβ/Smad signalling. UGDH and a key metabolite, UDP-GlcUA, may serve as prognostic markers. Targeting UGDH might be a promising strategy for HCC therapy.
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