ArticleScientific reports2016
Antithrombin controls tumor migration, invasion and angiogenesis by inhibition of enteropeptidase.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
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- Micropeptides Encoded by Noncoding RNAs: Biological Functions and Roles in Diseases.Research (Washington, D.C.) · 2025Review
- Tissue factor pathway-related biomarkers in liver cancer: activated factor VII-antithrombin complex and tissue factor mRNA levels are associated with mortality.Research and practice in thrombosis and haemostasis · 2024Article
- Advancements and Challenges of Nanostructured Lipid Carriers for Wound Healing Applications.International journal of nanomedicine · 2024Review
- Plant Serpins: Potential Inhibitors of Serine and Cysteine Proteases with Multiple Functions.Plants (Basel, Switzerland) · 2023Review
- Crosstalk between Circulating Tumor Cells and Plasma Proteins-Impact on Coagulation and Anticoagulation.Cancers · 2023Review
- Special Issue: Cancer Metastasis and Therapeutic Resistance.Biomedicines · 2023Article
- Venetoclax is a potent hepsin inhibitor that reduces the metastatic and prothrombotic phenotypes of hepsin-expressing colorectal cancer cells.Frontiers in molecular biosciences · 2023Article
- Designing bioresponsive nanomaterials for intracellular self-assembly.Nature reviews. Chemistry · 2022Review
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- The Cytotoxicity of RNase-Derived Peptides.Biomolecules · 2020Article
- A Novel Nanoproteomic Approach for the Identification of Molecular Targets Associated with Thyroid Tumors.Nanomaterials (Basel, Switzerland) · 2020Article
- Protein Corona Gold Nanoparticles Fingerprinting Reveals a Profile of Blood Coagulation Proteins in the Serum of HER2-Overexpressing Breast Cancer Patients.International journal of molecular sciences · 2020Article
- Exosomes in Angiogenesis and Anti-angiogenic Therapy in Cancers.International journal of molecular sciences · 2020Review
- Implications of Hemostasis Disorders in Patients with Critical Limb Ischemia-An In-Depth Comparison of Selected Factors.Journal of clinical medicine · 2020Article
- Quantitative proteomic analysis of bile in extrahepatic cholangiocarcinoma patients.Journal of Cancer · 2020Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antithrombin is a key inhibitor of the coagulation cascade, but it may also function as an anti-inflammatory, anti-angiogenic, anti-viral and anti-apoptotic protein. Here, we report a novel function of antithrombin as a modulator of tumor cell migration and invasion. Antithrombin inhibited enteropeptidase on the membrane surface of HT-29, A549 and U-87 MG cells. The inhibitory process required the activation of antithrombin by heparin, and the reactive center loop and the heparin binding domain were essential. Surprisingly, antithrombin non-covalently inhibited enteropeptidase, revealing a novel mechanism of inhibition for this serpin. Moreover, as a consequence of this inhibition, antithrombin was cleaved, resulting in a molecule with anti-angiogenic properties that reduced vessel-like formation of endothelial cells. The addition of antithrombin and heparin to U-87 MG and A549 cells reduced motility in wound healing assays, inhibited the invasion in transwell assays and the degradation of a gelatin matrix mediated by invadopodia. These processes were controlled by enteropeptidase, as demonstrated by RNA interference experiments. Carcinoma cell xenografts in nude mice showed in vivo co-localization of enteropeptidase and antithrombin. Finally, treatment with heparin reduced experimental metastasis induced by HT29 cells in vivo. In conclusion, the inhibition of enteropeptidase by antithrombin may have a double anti-tumor effect through inhibiting a protease involved in metastasis and generating an anti-angiogenic molecule.
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