ArticleHepatology (Baltimore, Md.)2014
A cell-surface β-hydroxylase is a biomarker and therapeutic target for hepatocellular carcinoma.
Article in Hepatology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 95 citations in OpenAlex.
- Enteroviral epitope mimicry enables NK cell-mediated targeting of ASPH in hepatocellular carcinoma.bioRxiv : the preprint server for biology · 2026Article
- Structural basis of the promiscuity of the unusual Fe(II) and 2-oxoglutarate dependent human aspartate/asparagine-β-hydroxylase.Nature communications · 2026Article
- Overexpression and prognostic value of aspartate β-hydroxylase in lung adenocarcinoma: a comprehensive study based on bioinformatics and clinical tissue sample validation.World journal of surgical oncology · 2026Article
- HRASLS2 promotes the growth and glycolysis of pancreatic cancer by enhancing the stability of ASPH.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Bile acid metabolism and invasion-related genes as therapeutic monitoring biomarkers in non-small cell lung cancer.Discover oncology · 2025Article
- Leukemia cells remodel bone marrow stromal cells to generate a protumoral microenvironment via the S100A8-NOX2-ROS signaling pathway.Scientific reports · 2025Article
- Article
- Derivatives of the Clinically Used HIF Prolyl Hydroxylase Inhibitor Desidustat Are Efficient Inhibitors of Human γ-Butyrobetaine Hydroxylase.Journal of medicinal chemistry · 2025Article
- Impact of Prenatal Dietary Soy on Cerebellar Neurodevelopment and Function in Experimental Fetal Alcohol Spectrum Disorder.Nutrients · 2025Article
- A novel hybrid approach to overcome defects of CE-SELEX and cell-SELEX in developing aptamers against aspartate β-hydroxylase.Research in pharmaceutical sciences · 2025Article
- Dietary Soy Preserves Cognitive Function in Experimental Fetal Alcohol Spectrum Disorder: Role of Increased Signaling through Notch and Gonadotropin Releasing Hormone Networks.Journal of behavioral and brain science · 2025Article
- Inhibition of Aspartate β-Hydroxylase Enhances Anti-Tumor Immunity.ImmunoTargets and therapy · 2025Article
- Multi-omics integration identifies ASPH and PTTG1 as potential causal drivers of lung adenocarcinoma progression and immune evasion.Frontiers in immunology · 2025Article
- Chondrosarcoma: Adjuvant Therapeutic Effects of the ASPH Small Molecule Inhibitor, SMI-1182, With Doxorubicin.Japanese journal of cancer and oncology research · 2025Article
- 10-hydroxy-2-decenoic acid prevents osteoarthritis by targeting aspartyl β hydroxylase and inhibiting chondrocyte senescence in male mice preclinically.Nature communications · 2024Article
- Aspartate β-Hydroxylase Is Upregulated in Head and Neck Squamous Cell Carcinoma and Regulates Invasiveness in Cancer Cell Models.International journal of molecular sciences · 2024Article
- Association between dietary soy prevention of fetal alcohol spectrum disorder and normalization of placental insulin and insulin-like growth factor signaling networks and downstream effector molecule expression.Gene & protein in disease · 2024Article
- Heterogeneous Response of Tumor Cell Lines to Inhibition of Aspartate β-hydroxylase.Journal of Cancer · 2024Article
- Aspartate β-hydroxylase Regulates Expression ofJournal of Cancer · 2024Article
- Cancer immunotherapy with enveloped self-amplifying mRNA CARG-2020 that modulates IL-12, IL-17 and PD-L1 pathways to prevent tumor recurrence.Acta pharmaceutica Sinica. B · 2024Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
unlabelledHepatocellular carcinoma (HCC) has a poor prognosis as a result of widespread intra- and extrahepatic metastases. There is an urgent need to understand signaling cascades that promote disease progression. Aspartyl-(asparaginyl)-β-hydroxylase (ASPH) is a cell-surface enzyme that generates enhanced cell motility, migration, invasion, and metastatic spread in HCC. We hypothesize that inhibition of its enzymatic activity could have antitumor effects. Small molecule inhibitors (SMIs) were developed based on the crystal structure of the ASPH catalytic site followed by computer-assisted drug design. Candidate compounds were tested for inhibition of β-hydroxylase activity and selected for their capability to modulate cell proliferation, migration, invasion, and colony formation in vitro and to inhibit HCC tumor growth in vivo using orthotopic and subcutaneous murine models. The biological effects of SMIs on the Notch signaling cascade were evaluated. The SMI inhibitor, MO-I-1100, was selected because it reduced ASPH enzymatic activity by 80% and suppressed HCC cell migration, invasion, and anchorage-independent growth. Furthermore, substantial inhibition of HCC tumor growth and progression was observed in both animal models. The mechanism(s) for this antitumor effect was associated with reduced activation of Notch signaling both in vitro and in vivo.
conclusionsThese studies suggest that the enzymatic activity of ASPH is important for hepatic oncogenesis. Reduced β-hydroxylase activity generated by the SMI MO-I-1100 leads to antitumor effects through inhibiting Notch signaling cascade in HCC. ASPH promotes the generation of an HCC malignant phenotype and represents an attractive molecular target for therapy of this fatal disease.
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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.