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)

Endo180 (CD280; MRC2; uPARAP) regulates collagen remodelling and chemotactic cell migration through cooperation with membrane type-1 matrix metalloproteinase (MT1-MMP), urokinase-type plasminogen activator receptor (uPAR) and urokinase-type plasminogen activator (uPA). One hundred and sixty nine prostate tissue sections clinically graded as benign prostatic hyperplasia (BPH) (n=29) or prostate cancer (PCA) with Gleason scores indicating low (< or =7(3+4); n=26), intermediate (7(4+3)-8; n=96) or high (9-10; n=19) clinical risk were immunofluorescently stained for Endo180, pan-cytokeratin (pCk), vimentin, MT1-MMP and uPAR-uPA. Quantification of % Endo180(+)/pCk(-) and Endo180(+)/pCk(+) cells in entire tissue cores revealed stromal (p=0.0001) and epithelial (p=0.0001) upregulation of Endo180 in PCA compared to BPH. Epithelial Endo180 expression was significantly different between the three clinical risk groups of PCA (p<0.05). Correlations with MT1-MMP and uPAR-uPA confirmed the functionality of Endo180 during PCA progression. This molecular evaluation is the first step in the exploration of Endo180 in PCA diagnosis and therapy.
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PMID:Endo180 expression with cofunctional partners MT1-MMP and uPAR-uPA is correlated with prostate cancer progression. 1911 15

The molecular interactions leading to organised, controlled extracellular matrix degradation are of central importance during growth, development and tissue repair, and when deregulated contribute to disease processes including cancer cell invasion. There are two major pathways for collagen degradation: one dependent on secreted and membrane-bound collagenases, the other on receptor-mediated collagen internalisation and intracellular processing. Despite the established importance of both pathways, the functional interaction between them is largely unknown. We demonstrate here, that the collagen internalisation receptor Endo180 (also known as CD280, uPARAP, MRC2) is a novel regulator of membrane-bound matrix metalloproteinase (MT1-MMP) activity, MT1-MMP-dependent MMP-2 activation and urokinase plasminogen activator (uPA) activity. We show close correlation between Endo180 expression, collagen accumulation and regulation of MT1-MMP cell-surface localisation and activity. We directly demonstrate, using collagen inhibition studies and non-collagen-binding mutants of Endo180, that the molecular mechanism underlying this regulation is the ability of Endo180 to bind and/or internalise collagens, rather than by acting as an interaction partner for pro-uPA and its receptor uPAR. These studies strongly support a functional interaction between two distinct collagen degradation pathways, define a novel mechanism regulating MT1-MMP activity and might have important implications for organised collagen clearance in the pericellular environment.
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PMID:Membrane type-1 matrix metalloproteinase activity is regulated by the endocytic collagen receptor Endo180. 1986