ArticleThe Journal of biological chemistry2009
Angioinhibitory action of NK4 involves impaired extracellular assembly of fibronectin mediated by perlecan-NK4 association.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Overexpression of NK4 gene in TU212 affects migratory activity in laryngeal squamous cell carcinoma.Frontiers in oncology · 2025Article
- The Evolving Landscape of the Molecular Epidemiology of Malignant Pleural Mesothelioma.Journal of clinical medicine · 2021Review
- Structural and Functional Insight Into the Glycosylation Impact Upon the HGF/c-Met Signaling Pathway.Frontiers in cell and developmental biology · 2020Review
- Inhibition of mesothelioma cancer stem-like cells with adenovirus-mediated NK4 gene therapy.International journal of cancer · 2015Article
- A clinical protocol to inhibit the HGF/c-Met pathway for malignant mesothelioma with an intrapleural injection of adenoviruses expressing the NK4 gene.SpringerPlus · 2015Article
- Regulation of hepatocyte growth factor in mice with pneumonia by peptidases and trans-alveolar flux.PloS one · 2015Article
- Epithelial-mesenchymal status influences how cells deposit fibrillin microfibrils.Journal of cell science · 2014Article
- Molecular targeting of hepatocyte growth factor by an antagonist, NK4, in the treatment of rheumatoid arthritis.Arthritis research & therapy · 2013Article
- NK4 gene therapy inhibits HGF/Met-induced growth of human cholangiocarcinoma cells.Digestive diseases and sciences · 2013Article
- Gene therapy for malignant mesothelioma: current prospects and challenges.Cancer gene therapy · 2013Review
- HGF-MET cascade, a key target for inhibiting cancer metastasis: the impact of NK4 discovery on cancer biology and therapeutics.International journal of molecular sciences · 2013Article
- NK4 therapy: a new approach to target angiogenesis and inflammation in rheumatoid arthritis.Arthritis research & therapy · 2013Article
- Glycoconjugates and related molecules in human vascular endothelial cells.International journal of vascular medicine · 2013Review
- A potential therapeutic strategy for malignant mesothelioma with gene medicine.BioMed research international · 2013Review
- Perlecan maintains microvessel integrity in vivo and modulates their formation in vitro.PloS one · 2013Article
- Identification of mannose receptor as receptor for hepatocyte growth factor β-chain: novel ligand-receptor pathway for enhancing macrophage phagocytosis.The Journal of biological chemistry · 2012Article
- Characterization of an Oncolytic Adenovirus Vector Constructed to Target the cMet Receptor.Oncolytic virotherapyArticle
- MET molecular mechanisms and therapies in lung cancer.Cell adhesion & migrationReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NK4, a fragment of hepatocyte growth factor (HGF), exerts bifunctional action as a competitive antagonist against HGF and its receptor c-Met and an angiogenesis inhibitor. Here we studied the anti-angiogenic mechanism of NK4. In cultured human endothelial cells, NK4 inhibited DNA synthesis induced not only by HGF but also by either basic fibroblast growth factor or vascular endothelial growth factor. Even if c-Met expression was diminished by small interference RNA, NK4 inhibited basic fibroblast growth factor-induced DNA synthesis, indicating that anti-angiogenic action of NK4 is c-Met-independent. Affinity purification with NK4-immobilized beads revealed that NK4 binds to perlecan. Consistent with this, NK4 colocalized with perlecan in endothelial cells. Perlecan is a multidomain heparan sulfate proteoglycan that interacts with basement membrane components such as fibronectin. NK4 inhibited extracellular assembly of fibronectin, by which fibronectin-dependent endothelial cell spreading was inhibited by NK4. Knockdown of perlecan expression by small interference RNA significantly abrogated the inhibitory effect of NK4 on fibronectin assembly and cell spreading. In NK4-treated endothelial cells, tyrosine phosphorylation of focal adhesion kinase and Rac activation were reduced, whereas overexpression of activated Rac recovered the DNA synthesis in NK4-treated endothelial cells. These results indicate that the association between NK4 and perlecan impairs fibronectin assembly, thereby inhibiting anchorage-dependent signaling. The identified mechanism for angiostatic action provides further proof of significance for NK4 in the treatment of cancer and potentially for vascular regulation as well.
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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.