ArticleBMC cancer2016
Activated thrombin-activatable fibrinolysis inhibitor (TAFIa) attenuates breast cancer cell metastatic behaviors through inhibition of plasminogen activation and extracellular proteolysis.
Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 37 citations in OpenAlex.
- Thrombomodulin: A key regulator of intravascular blood coagulation, fibrinolysis, and inflammation, and a treatment for disseminated intravascular coagulation.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025Review
- Exploitation of the fibrinolytic system by B-cell acute lymphoblastic leukemia and its therapeutic targeting.Nature communications · 2024Article
- Dependence of clot structure and fibrinolysis on apixaban and clotting activator.Research and practice in thrombosis and haemostasis · 2024Article
- Underlying Mechanisms of Thrombosis Associated with Cancer and Anticancer Therapies.Current treatment options in oncology · 2024Review
- Profibrinolytic effects of rivaroxaban are mediated by thrombin-activatable fibrinolysis inhibitor and are attenuated by a naturally occurring stabilizing mutation in enzyme.Journal of thrombosis and thrombolysis · 2023Article
- Key therapeutic targets implicated at the early stage of hepatocellular carcinoma identified through machine-learning approaches.Scientific reports · 2023Article
- Comprehensive analysis for clarifying transcriptomics landscapes of spread through air spaces in lung adenocarcinoma.Frontiers in genetics · 2022Article
- Thrombomodulin expression impacts the recurrence and long-term survival in pancreatic cancer.Annals of gastroenterological surgery · 2021Article
- A Coagulation-Related Gene-Based Prognostic Model for Invasive Ductal Carcinoma.Frontiers in genetics · 2021Article
- Article
- Comparative Analysis of Systemic and Tumor Microenvironment Proteomes From Children With B-Cell Acute Lymphocytic Leukemia at Diagnosis and After Induction Treatment.Frontiers in oncology · 2020Article
- Identification and validation of stromal-tumor microenvironment-based subtypes tightly associated with PD-1/PD-L1 immunotherapy and outcomes in patients with gastric cancer.Cancer cell international · 2020Article
- TAFI deficiency causes maladaptive vascular remodeling after hemophilic joint bleeding.JCI insight · 2019Article
- The coagulome and the oncomir: impact of cancer-associated haemostatic dysregulation on the risk of metastasis.Clinical & experimental metastasis · 2018Review
- Epsilon-aminocaproic acid prevents high glucose and insulin induced-invasiveness in MDA-MB-231 breast cancer cells, modulating the plasminogen activator system.Molecular and cellular biochemistry · 2018Article
- Activated thrombin-activatable fibrinolysis inhibitor attenuates the angiogenic potential of endothelial cells: potential relevance to the breast tumour microenvironment.Clinical & experimental metastasis · 2017Article
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8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThrombin activatable fibrinolysis inhibitor (TAFI) is a plasma zymogen, which can be converted to activated TAFI (TAFIa) through proteolytic cleavage by thrombin, plasmin, and most effectively thrombin in complex with the endothelial cofactor thrombomodulin (TM). TAFIa is a carboxypeptidase that cleaves carboxyl terminal lysine and arginine residues from protein and peptide substrates, including plasminogen-binding sites on cell surface receptors. Carboxyl terminal lysine residues play a pivotal role in enhancing cell surface plasminogen activation to plasmin. Plasmin has many critical functions including cleaving components of the extracellular matrix (ECM), which enhances invasion and migration of cancer cells. We therefore hypothesized that TAFIa could act to attenuate metastasis.
methodsTo assess the role of TAFIa in breast cancer metastasis, in vitro migration and invasion assays, live cell proteolysis and cell proliferation using MDA-MB-231 and SUM149 cells were carried out in the presence of a TAFIa inhibitor, recombinant TAFI variants, or soluble TM.
resultsInhibition of TAFIa with potato tuber carboxypeptidase inhibitor increased cell invasion, migration and proteolysis of both cell lines, whereas addition of TM resulted in a decrease in all these parameters. A stable variant of TAFIa, TAFIa-CIIYQ, showed enhanced inhibitory effects on cell invasion, migration and proteolysis. Furthermore, pericellular plasminogen activation was significantly decreased on the surface of MDA-MB-231 and SUM149 cells following treatment with various concentrations of TAFIa.
conclusionsTaken together, these results indicate a vital role for TAFIa in regulating pericellular plasminogen activation and ultimately ECM proteolysis in the breast cancer microenvironment. Enhancement of TAFI activation in this microenvironment may be a therapeutic strategy to inhibit invasion and prevent metastasis of breast cancer cells.
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