ArticleOncogenesis2020
Non-metabolic role of UCK2 links EGFR-AKT pathway activation to metastasis enhancement in hepatocellular carcinoma.
Article in Oncogenesis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Network Pharmacology and Integrated Experimental Evidence Demonstrate That Ophiopogonin D Suppresses Hepatocellular Carcinoma Progression via the UCK2-SLC7A11 Axis.Food science & nutrition · 2026Article
- Uridine-Cytidine Kinase 2 (UCK2)/Uridine-Cytidine Kinase Like 1 (UCKL1) complex exacerbates the differentiation of myocardial fibroblasts via TRIM21/Smurf2/Smad3 pathway after myocardial infarction.Molecular biomedicine · 2025Article
- Uridine-cytidine kinase 2 as a novel potential prognostic and therapeutic biomarker in gastric cancer.Translational cancer research · 2025Article
- Uridine as a hub in cancer metabolism and RNA biology.Experimental & molecular medicine · 2025Review
- Comprehensive multi-omics analysis of nucleotide metabolism: elucidating the role and prognostic significance of UCK2 in bladder cancer.Functional & integrative genomics · 2025Article
- The protection of UCK2 protein stability by GART maintains pyrimidine salvage synthesis for HCC growth under glucose limitation.Oncogene · 2025Article
- PET imaging of hepatocellular carcinoma with [EJNMMI research · 2025Article
- CircUCK2(2,3) promotes cancer progression and enhances synergistic cytotoxicity of lenvatinib with EGFR inhibitors via activating CNIH4-TGFα-EGFR signaling.Cellular & molecular biology letters · 2025Article
- Identification and validation of icaritin-associated prognostic genes in hepatocellular carcinoma through network pharmacology, bioinformatics analysis, and cellular experiments.Frontiers in immunology · 2025Article
- Glucose limitation protects cancer cells from apoptosis induced by pyrimidine restriction and replication inhibition.Nature metabolism · 2024Article
- UCK2 promotes intrahepatic cholangiocarcinoma progression and desensitizes cisplatin treatment by PI3K/AKT/mTOR/autophagic axis.Cell death discovery · 2024Article
- Immune- and metabolism-related gene signature analysis uncovers the prognostic and immune microenvironments of hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2024Article
- A prognostic and immune related risk model based on zinc homeostasis in hepatocellular carcinoma.iScience · 2024Article
- Reprogramming of pyrimidine nucleotide metabolism supports vigorous cell proliferation of normal and malignant T cells.Blood advances · 2024Article
- Integrative Analyses of Pyrimidine Salvage Pathway-Related Genes Revealing the Associations Between UPP1 and Tumor Microenvironment.Journal of inflammation research · 2024Article
- Cellular senescence throws new insights into patient classification and pharmacological interventions for clinical management of hepatocellular carcinoma.World journal of gastrointestinal oncology · 2023Article
- M7G methylated core genes (METTL1 and WDR4) and associated RNA risk signatures are associated with prognosis and immune escape in HCC.BMC medical genomics · 2023Article
- The Role of PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma Metabolism.International journal of molecular sciences · 2023Review
- Comprehensive Analysis of METTLs (METTL1/13/18/21A/23/25/2A/2B/5/6/9) and Associated mRNA Risk Signature in Hepatocellular Carcinoma.Analytical cellular pathology (Amsterdam) · 2023Article
- Targeting uridine-cytidine kinase 2 induced cell cycle arrest through dual mechanism and could improve the immune response of hepatocellular carcinoma.Cellular & molecular biology letters · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Up-regulation of Uridine-cytidine kinase 2 (UCK2), a rate-limiting enzyme of the pyrimidine salvage pathway, has been suggested in HCC, but the detailed molecular mechanisms and therapic role of UCK2 remain elusive. Bioinformatic analyses revealed that UCK2 might be a key up-regulated metabolic gene in HCCs. The expressional pattern and prognostic value of UCK2 were further examined in a large number of clinical samples. Functional assays based on site-directed mutagenesis showed that UCK2 promoted cell proliferation in a metabolic manner, but non-catalytically facilitates HCC metastasis. Mechanistically, in response to EGF, UCK2 interacted with EGFR to block EGF-induced EGFR ubiquitination and degradation, which resulted in elevated EGFR-AKT pathway activation and metastasis enhancement in HCCs. Concurrent pharmacological targeting on UCK2 and EGFR showed synergistic effects on HCC treatment. This study disclosed the non-metabolic role of UCK2 and suggested the therapeutic potential of concurrent blocking the metabolic and non-metabolic roles of UCK2 in HCC treatment.
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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.