ArticleScientific reports2015
Angiogenin secretion from hepatoma cells activates hepatic stellate cells to amplify a self-sustained cycle promoting liver cancer.
Article in Scientific reports, 2015. 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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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, 51 citations in OpenAlex.
- Targeting Hepatic Stellate Cells for the Prevention and Treatment of Liver Cirrhosis and Hepatocellular Carcinoma: Strategies and Clinical Translation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Assay for ribosome stimulation of angiogenin nuclease activity.Methods in enzymology · 2025Article
- Review
- Article
- Combination of Phenethyl Isothiocyanate and Dasatinib Inhibits Hepatocellular Carcinoma Metastatic Potential through FAK/STAT3/Cadherin Signalling and Reduction of VEGF Secretion.Pharmaceutics · 2023Article
- Site-specific ubiquitination of VDAC1 restricts its oligomerization and mitochondrial DNA release in liver fibrosis.Experimental & molecular medicine · 2023Article
- Emerging biological functions of ribonuclease 1 and angiogenin.Critical reviews in biochemistry and molecular biology · 2022Review
- Review
- Angiogenin (ANG)-Ribonuclease Inhibitor (RNH1) System in Protein Synthesis and Disease.International journal of molecular sciences · 2021Review
- Increase in CD4Oncology letters · 2020Article
- Angiogenin regulates PKD activation and COX-2 expression induced by TNF-α and bradykinin in the colonic myofibroblast.Biochemical and biophysical research communications · 2020Article
- Article
- A Functional Role of GAS6/TAM in Nonalcoholic Steatohepatitis Progression Implicates AXL as Therapeutic Target.Cellular and molecular gastroenterology and hepatology · 2020Article
- Hepatic Stellate Cells and Hepatocarcinogenesis.Frontiers in cell and developmental biology · 2020Review
- Stromal fibroblast growth factor 2 reduces the efficacy of bromodomain inhibitors in uveal melanoma.EMBO molecular medicine · 2019Article
- Angiogenin Upregulation Independently Predicts Unfavorable Overall Survival in Proneural Subtype of Glioblastoma.Technology in cancer research & treatment · 2019Article
- Selective Export into Extracellular Vesicles and Function of tRNA Fragments during T Cell Activation.Cell reports · 2018Article
- A novel ligand-receptor relationship between families of ribonucleases and receptor tyrosine kinases.Journal of biomedical science · 2018Review
- Human angiogenin is a potent cytotoxin in the absence of ribonuclease inhibitor.RNA (New York, N.Y.) · 2018Article
- Endothelial Progenitor Cell Secretome and Oligovascular Repair in a Mouse Model of Prolonged Cerebral Hypoperfusion.Stroke · 2018Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Hepatocellular carcinoma (HCC) frequently develops in a pro-inflammatory and pro-fibrogenic environment with hepatic stellate cells (HSCs) remodeling the extracellular matrix composition. Molecules secreted by liver tumors contributing to HSC activation and peritumoral stromal transformation remain to be fully identified. Here we show that conditioned medium from HCC cell lines, Hep3B and HepG2, induced primary mouse HSCs transdifferentiation, characterized by profibrotic properties and collagen modification, with similar results seen in the human HSC cell line LX2. Moreover, tumor growth was enhanced by coinjection of HepG2/LX2 cells in a xenograft murine model, supporting a HCC-HSC crosstalk in liver tumor progression. Protein microarray secretome analyses revealed angiogenin as the most robust and selective protein released by HCC compared to LX2 secreted molecules. In fact, recombinant angiogenin induced in vitro HSC activation requiring its nuclear translocation and rRNA transcriptional stimulation. Moreover, angiogenin antagonism by blocking antibodies or angiogenin inhibitor neomycin decreased in vitro HSC activation by conditioned media or recombinant angiogenin. Finally, neomycin administration reduced tumor growth of HepG2-LX2 cells coinjected in mice. In conclusion, angiogenin secretion by HCCs favors tumor development by inducing HSC activation and ECM remodeling. These findings indicate that targeting angiogenin signaling may be of potential relevance in HCC management.
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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.