Urokinase receptors (uPAR) were initially thought to function simply as a mechanism to concentrate the urokinase/plasmin system toward the cell surface. However, extensive evidence has accumulated that this glycolipid-anchored receptor also functions in both the adhesive and signaling pathways of many migratory cells. Mechanisms by which uPAR exercises these functions involve complexing with other membrane proteins for signal transduction. One set of functional partners for uPAR on the cell surface are integrins. Recent studies point to important structural features of uPAR:integrin interactions, indicating uPAR to be a cis-acting integrin ligand. In vivo data reveal altered integrin function and cell migration when uPAR:integrin interactions are impaired. Together these observations support the idea that uPAR:integrin interactions may be a focal point of intervention in pathobiology where integrin function is crucial, such as tumor metastasis.
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Factor XII signaling via uPAR-integrin β1 axis promotes tubular senescence in diabetic kidney disease.
Nat Commun
September 2024
Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig Medical Center, Leipzig, Germany.
Article Synopsis
- - Coagulation factor XII (FXII) is linked to thrombosis and inflammation and is found in increased levels in diabetes and diabetic kidney disease (DKD), but its specific role in DKD was unclear until now.
- - The study reveals that FXII is present in kidney tubular cells, correlating with kidney dysfunction in DKD patients; mice lacking FXII showed protection against kidney damage from high blood sugar.
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Elevated PLAUR is observed in the airway epithelium of asthma patients and blocking improves barrier integrity.
Clin Transl Allergy
October 2023
Centre for Respiratory Research, NIHR Respiratory Biomedical Research Centre, School of Medicine, Biodiscovery Institute, University Park, University of Nottingham, Nottingham, UK.
Background: Expression of the urokinase plasminogen activator receptor (uPAR) is elevated in the airway epithelium in asthma; however, the contribution of uPAR to asthma pathogenesis and scope for therapeutic targeting remains unknown.
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Urokinase Receptor uPAR Downregulation in Neuroblastoma Leads to Dormancy, Chemoresistance and Metastasis.
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National Cardiology Research Center of the Ministry of Health of the Russian Federation, Institute of Experimental Cardiology, 121552 Moscow, Russia.
uPAR is a membrane receptor that binds extracellular protease urokinase, contributes to matrix remodeling and plays a crucial role in cellular adhesion, proliferation, survival, and migration. uPAR overexpression in tumor cells promotes mitogenesis, opening a prospective avenue for targeted therapy. However, uPAR targeting in cancer has potential risks.
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EBioMedicine
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Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale G.B. Morgagni, 50, 50134 Florence, Italy.
Background: BRAF inhibitor (BRAF-I) therapy for melanoma patients harboring the V600E mutation is initially highly effective, but almost all patients relapse within a few months. Understanding the molecular mechanisms behind BRAF-I responsiveness and acquired resistance is therefore an important issue. Here we assessed the role of urokinase type plasminogen activator receptor (uPAR) as a potentially valuable biomarker in the acquisition of BRAF-I resistance in V600E mutant melanoma cells.
View Article and Find Full Text PDFMature and progenitor endothelial cells perform angiogenesis also under protease inhibition: the amoeboid angiogenesis.
J Exp Clin Cancer Res
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Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Section of Experimental Pathology and Oncology, Viale G.B. Morgagni, 50-50134, Florence, Italy.
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Methods: A cocktail of physiologic inhibitors (Ph-C) of serine-proteases, metallo-proteases and cysteine-proteases, mimicking the physiological environment that cells encounter during their migration within the angiogenesis sites was used to induce amoeboid style migration of Endothelial colony forming cells (ECFCs) and mature endothelial cells (ECs).
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