ArticleOncotarget2016
Thrombomodulin promotes focal adhesion kinase activation and contributes to angiogenesis by binding to fibronectin.
Article in Oncotarget, 2016. 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 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
18 citing papers in PubMed, 30 citations in OpenAlex.
- Identification of an Anoikis-Related Gene Signature to Predict the Prognosis in Patients With Oral Squamous Cell Carcinoma.International dental journal · 2026Article
- Thrombomodulin facilitates melanoma progression via FAK- and ezrin-mediated phenotypic plasticity.Journal of biomedical science · 2026Article
- A guide to building the matrisome interactome: from computational predictions to experimental validation.The FEBS journal · 2026Review
- The Multifaceted Roles of Thrombomodulin: Anti-coagulation, Anti-inflammation, and Anti-tumor Potential.Current pharmaceutical design · 2025Review
- Hemostasis and endothelial functionality: the double face of coagulation factors.Haematologica · 2024Review
- Group XIV C-type lectins: emerging targets in tumor angiogenesis.Angiogenesis · 2024Review
- Interference in melanoma CD248 function reduces vascular mimicry and metastasis.Journal of biomedical science · 2022Article
- Upregulated miR-18a-5p in Colony Forming Unit-Hill's in Subclinical Cardiovascular Disease and Metformin Therapy; MERIT Study.Biomedicines · 2022Article
- Circulating Thrombomodulin: Release Mechanisms, Measurements, and Levels in Diseases and Medical Procedures.TH open : companion journal to thrombosis and haemostasis · 2022Review
- A glimpse into the past: phylogenesis and protein domain analysis of the group XIV of C-type lectins in vertebrates.BMC genomics · 2022Article
- Cancer immune profiling unveils biomarkers, immunological pathways, and cell type score associated with glioblastoma patients' survival.Therapeutic advances in medical oncology · 2022Article
- The Lectin-Like Domain of Thrombomodulin Inhibits β1 Integrin-Dependent Binding of Human Breast Cancer-Derived Cell Lines to Fibronectin.Biomedicines · 2021Article
- C-type lectin family XIV members and angiogenesis.Oncology letters · 2019Review
- C-type lectin domain group 14 proteins in vascular biology, cancer and inflammation.The FEBS journal · 2019Review
- A thrombomodulin-like gene is crucial to the collective migration of epibolic blastomeres during germ layer formation and organogenesis in zebrafish.Journal of biomedical science · 2019Article
- C-type lectins in immunity and homeostasis.Nature reviews. Immunology · 2018Review
- The chondroitin sulfate moiety mediates thrombomodulin-enhanced adhesion and migration of vascular smooth muscle cells.Journal of biomedical science · 2018Article
- Oridonin inhibits migration, invasion, adhesion and TGF-β1-induced epithelial-mesenchymal transition of melanoma cells by inhibiting the activity of PI3K/Akt/GSK-3β signaling pathway.Oncology letters · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angiogenesis promotes tumor growth and metastasis. Cell adhesion molecules interact with the extracellular matrix (ECM) and increase cell adhesion and migration during angiogenesis. Thrombomodulin (TM) is a cell surface transmembrane glycoprotein expressed in endothelial cells. However, the function and significance of TM in cell-matrix interactions and angiogenesis remain unclear. Here, we first demonstrated that recombinant lectin-like domain of TM interacts with an ECM protein, fibronectin, and identified the N-terminal 70-kDa domain of fibronectin as the TM-binding site. Exogenous expression of TM in TM-deficient A2058 melanoma cells enhanced cell adhesion and migration on fibronectin and invasion on Matrigel. In addition, TM increased focal adhesion kinase (FAK) phosphorylation and matrix metalloproteinase-9 production. In mice bearing subcutaneous B16F10 melanoma tumors, immunofluorescence analysis indicated that TM was highly expressed and co-localized with fibronectin on the tumor vasculature. The interaction between TM and fibronectin in tumor blood vessels was also validated by the proximity ligation assay. In human umbilical vein endothelial cells, up-regulation of TM by vascular endothelial growth factor (VEGF), a tumor angiogenic factor, promoted cell adhesion and tube formation, whereas TM knockdown by RNA interference attenuated VEGF-induced cell adhesion and tube formation. In summary, TM promotes angiogenesis by enhancing cell adhesion, migration, and FAK activation through interaction with fibronectin. TM may represent a novel target for inhibiting tumor angiogenesis.
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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.