ArticleMolecular and cellular biology2010
Downregulation of thrombomodulin, a novel target of Snail, induces tumorigenesis through epithelial-mesenchymal transition.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- Regulation of cell proliferation and migration by p62 through stabilization of Twist1.Proceedings of the National Academy of Sciences of the United States of America · 2014Trial
- Zeb1 Is a Determinant of EMT in Human MDA-MB-231 Breast Cancer Cells and M13-MDA231 Tumor Hybrids.International journal of molecular sciences · 2026Article
- Decoding the Snail transcriptional network: its role in cancer progression and therapy.Biology direct · 2026Review
- Thrombomodulin Mitigates the Progression of Hepatocellular Carcinoma in Steatotic Liver.Journal of hepatocellular carcinoma · 2026Article
- Thrombomodulin: a multifunctional receptor modulating the endothelial quiescence.Journal of thrombosis and haemostasis : JTH · 2024Review
- Thrombomodulin Regulates PTEN/AKT Signaling Axis in Endothelial Cells.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Autophagy regulates tumor growth and metastasis.bioRxiv : the preprint server for biology · 2023Article
- Chondrocyte Thrombomodulin Protects against Osteoarthritis.International journal of molecular sciences · 2023Article
- Activated protein C inhibits mesothelial-to-mesenchymal transition in experimental peritoneal fibrosis.Journal of thrombosis and haemostasis : JTH · 2023Article
- Thrombomodulin expression impacts the recurrence and long-term survival in pancreatic cancer.Annals of gastroenterological surgery · 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
- Thrombomodulin Regulation of Mitogen-Activated Protein Kinases.International journal of molecular sciences · 2019Review
- SIRT6 drives epithelial-to-mesenchymal transition and metastasis in non-small cell lung cancer via snail-dependent transrepression of KLF4.Journal of experimental & clinical cancer research : CR · 2018Article
- Plasminogen/thrombomodulin signaling enhances VEGF expression to promote cutaneous wound healing.Journal of molecular medicine (Berlin, Germany) · 2018Article
- The chondroitin sulfate moiety mediates thrombomodulin-enhanced adhesion and migration of vascular smooth muscle cells.Journal of biomedical science · 2018Article
- Article
- Myeloid thrombomodulin lectin-like domain inhibits osteoclastogenesis and inflammatory bone loss.Scientific reports · 2016Article
- Thrombomodulin promotes diabetic wound healing by regulating toll-like receptor 4 expression.The Journal of investigative dermatology · 2015Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The expression of thrombomodulin (TM), a calcium-dependent adhesion molecule, is frequently downregulated in various cancer types. However, the mechanism responsible for the low expression level of TM in tumorigenesis is unknown. Here, an inverse expression of TM and Snail was detected in different cancer cell lines. We further confirmed this inverse relation using the epithelial-mesenchymal transition cell model in HaCaT and A431 cells. We demonstrated that Snail suppressed TM expression by binding to E-box (CACCTG) in TM promoter. Moreover, TM knockdown by short hairpin RNA disrupted E-cadherin-mediated cell junctions and contributed to tumorigenesis. In the calcium switch assay, E-cadherin lost the ability to associate with β-catenin and accumulated in cytoplasm in TM knockdown cells. Meanwhile, wound healing and invasive assays showed that TM knockdown promoted cell motility. A subcutaneous injection of TM knockdown transfectants into immunocompromised mice induced squamous cell carcinoma-like tumors. Besides, forced expression of murine TM in TM knockdown cells made the cells reassume epithelium-like morphology and increased calcium-dependent association of E-cadherin and β-catenin. In conclusion, TM, a novel downstream target of Snail in epithelial-mesenchymal transition, is required for maintaining epithelial morphology and functions as a tumor suppressor.
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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.