ArticleSignal transduction and targeted therapy2020
Thrombin is a therapeutic target for non-small-cell lung cancer to inhibit vasculogenic mimicry formation.
Article in Signal transduction and targeted therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Vasculogenic mimicry in non-small cell lung cancer: a systematic review.Frontiers in oncology · 2025Pooled it
- RNA methyltransferase NSUN2 enhances vasculogenic mimicry and malignant progression of cervical cancer through upregulation of MMP-9.Oncology letters · 2026Article
- The unseen architects of metastasis: coagulation factors in pre-metastatic niche development.Cell communication and signaling : CCS · 2026Review
- Emerging roles of haemostatic proteins as markers of disease progression and prognosis in breast cancer.Exploration of targeted anti-tumor therapy · 2026Review
- Proteome-wide Mendelian randomization and colocalization analysis uncovers druggable targets for lung cancer across multiple phenotypes and complications.Discover oncology · 2025Article
- Cancer-associated fibroblasts expressing FSTL3 promote vasculogenic mimicry formation and drive colon cancer malignancy.Cell death & disease · 2025Article
- Recombinant hirudin and PAR-1 regulate macrophage polarisation status in diffuse large B-cell lymphoma.BMC biotechnology · 2024Article
- Aptamer-Based DNA Allosteric Switch for Regulation of Protein Activity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Hemostasis and endothelial functionality: the double face of coagulation factors.Haematologica · 2024Review
- Article
- The Clinical Significance and Involvement in Molecular Cancer Processes of Chemokine CXCL1 in Selected Tumors.International journal of molecular sciences · 2024Review
- CD146Cell communication and signaling : CCS · 2024Article
- Research Progress on the Anticancer Activity of Plant Polysaccharides.Recent patents on anti-cancer drug discovery · 2024Review
- Changing profile of lung cancer clinical characteristics in China: Over 8-year population-based study.Chinese medical journal pulmonary and critical care medicine · 2023Article
- RIPK1-dependent necroptosis promotes vasculogenic mimicry formation via eIF4E in triple-negative breast cancer.Cell death & disease · 2023Article
- Microparticle Phosphatidylserine Mediates Coagulation: Involvement in Tumor Progression and Metastasis.Cancers · 2023Review
- [Research Progress on Pathogenic Mechanism and Potential Therapeutic Drugs of Idiopathic Pulmonary Fibrosis Complicated with Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2022Article
- Orchestrated expression of vasculogenic mimicry and laminin-5γ2 is an independent prognostic marker in oral squamous cell carcinoma.International journal of experimental pathology · 2022Article
- Microbial metabolite deoxycholic acid promotes vasculogenic mimicry formation in intestinal carcinogenesis.Cancer science · 2022Article
- LOXL1-AS1 communicating with TIAR modulates vasculogenic mimicry in glioma via regulation of the miR-374b-5p/MMP14 axis.Journal of cellular and molecular medicine · 2022Article
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10 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Tumor cells transform into endothelial cells by epithelial-to-mesenchymal transition, which is characterized by vasculogenic mimicry (VM). VM not only accelerates tumor progression but also increases drug-induced resistance. However, very little is currently known about the molecular determinants that enable VM. Targeting VM might bring a new breakthrough in cancer treatment. Thrombin is the key enzyme of the blood coagulation system and could contribute to tumor progression. Nevertheless, the association between thrombin and VM formation remains largely unknown. We found that VM was associated with the overall survival of non-small-cell lung cancer (NSCLC) patients, and that thrombin expression was closely related to VM formation. This research revealed that thrombin induced VM formation via PAR-1-mediated NF-κB signaling cascades. The novel thrombin inhibitors r-hirudin and DTIP inhibited VM formation and spontaneous metastases in subcutaneous tumors. Clinical pathological analysis confirmed that NSCLC patients with thrombin-positive/PAR-1-high expression had the poorest prognosis and were the most likely to form VM. The promotional activity of thrombin in VM formation and tumor metastasis was abolished in PAR-1-deficient NSCLC cells. The EGFR inhibitor gefitinib had no effect on VM and increased VEGF expression in tumors. The combination therapy of DTIP and gefitinib achieved a better therapeutic effect than either agent alone. This study is the first to illustrate that thrombin substantially contributes, together with PAR-1, to VM formation and to illustrate that VM might be a target of r-hirudin and DTIP to suppress tumor progression. The anticoagulants r-hirudin and DTIP could be employed for antitumor therapy. Combination therapy with DTIP with an EGFR inhibitor might achieve superior therapeutic effects.
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