Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activated protein C (APC) and protein C inhibitor (PCI) are the major components of the anticoagulant protein C pathway. Recently, APC and PCI have been demonstrated to play many roles not only in the regulation of hemostasis but also in cell inflammation, proliferation, apoptosis, tumor cell migration, invasion, and metastasis. Here we summarize the role of APC and PCI in malignancy. APC increases migration of ovarian cancer cells and choriocarcinoma cells in a Transwell invasion assay in the presence of plasminogen activator inhibitor (PAI)-1; this finding suggests that APC stimulates urokinase-type plasminogen activator (uPA) by forming a complex with PAI-1 leading to activation of extracellular matrix proteases and increased invasion. It was recently reported that APC, independent of PAI-1, may increase invasion and chemotaxis of breast cancer cells by activating specific signaling pathways through endothelial protein C receptor (EPCR) and protease-activated receptor (PAR)-1. APC also increased proliferation of vascular endothelial cells and angiogenesis by EPCR-mediated activation of mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), and endothelial nitric oxide synthase (eNOS) pathways. On the other hand, we have previously reported that both uPA and PCI are synthesized in renal proximal tubular epithelial cells (RPTECs) and that PCI expression in RPTEC-derived tumor cells is significantly decreased compared with normal RPTECs. The RPTEC-derived renal carcinoma cell line Caki-1 also showed decreased expression of PCI. PCI inhibited in vitro invasive activity of Caki-1 and breast cancer cells by its protease inhibitory activity. However, PCI was found to inhibit the growth and metastatic potential of breast cancer cells independent of its protease inhibitory activity in severe combined immunodeficient mice. PCI can also inhibit angiogenesis in vivo and in vitro assays independent of its protease inhibitory activity. Overall, these data show that APC promotes tumor cell invasion by EPCR-mediated and PAR-1-mediated protease activity and that PCI inhibits tumor cell invasion in vitro by its protease inhibitory activity and suppresses tumor cell growth, metastasis, and angiogenesis independent of its protease inhibitory activity.
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PMID:Protein C and its inhibitor in malignancy. 1800 Jul 93

Proteomics is a novel molecular profiling technology. It is mainly concerned with determining the structure, expression, localization, biochemical activity, interactions, and cellular roles of any proteins. Clinical research hopes to benefit from proteomics in the identification of new drug targets and the development of new diagnostic markers. Better to understand the mechanisms by which ascofuranone (AF), an isoprenoid antibiotic, regulates physiological or pathological events and induces responses in the pharmacological treatment of cancer, we performed differential analysis of the human osteosarcoma cells U2OS proteomes in response to this agent. The U2OS cell proteomes with and without treatment with AF were compared using two-dimensional electrophoresis, matrix-assisted laser desorption/ionization mass spectrometry, and bioinformatics. The largest differences in protein expression were observed for hydroxyindole O-methyltransferase, syntaxin-binding protein 1, the matrix metalloproteinase (MMP)-2, urokinase receptor, and endothelial protein C receptor. Changes in expression and activity of some selected proteins were confirmed by Western blotting, zymography, and reverse transcription-polymerase chain reaction analysis. In particular, we observed downregulated tumor growth related-proteins such as MMP-2 and endothelial protein C receptor. According to these results, AF might be useful as a potent chemotherapeutic agent.
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PMID:Proteome profiling of U2OS cell line in response to a prenylphenol antibiotic isolated from a phytopathogenic fungus. 1875 62