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Plasmin Produces an E-Cadherin Fragment That Stimulates Cancer Cell Invasion

  • Filip Ryniers , Christophe Stove , Marc Goethals , Liesbeth Brackenier , Veerle Noë , Marc Bracke , Joël Vandekerckhove , Marc Mareel and Erik Bruyneel
Published/Copyright: June 1, 2005
Biological Chemistry
From the journal Volume 383 Issue 1

Abstract

Matrix metalloproteases from the cell surface cleave an 80 kDa Ecadherin fragment (sECAD) that induces invasion of cancer cells into collagen type I and inhibits cellular aggregation. Conditioned media from MDCKts.srcCl2 cells at 40 C and 35 C, PCm.src5 and COLO-16 cells at 37 C contained spontaneously released sECAD; these 48 h old conditioned media were capable of inhibiting Ecadherin functions in a paracrine way. Here we show direct cleavage of the extracellular domain of Ecadherin by the serine protease plasmin. sECAD released by plasmin inhibits Ecadherin functions as evidenced by induction of invasion into collagen type I and inhibition of cellular aggregation. This functional inhibition by sECAD was reversed by aprotinin or by immunoadsorption on protein Sepharose 4 fast flow beads with antibodies against the extracellular part of Ecadherin. Our results demonstrate that plasmin produces extracellular Ecadherin fragments which regulate Ecadherin function in cells containing an intact Ecadherin/ catenin complex.

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Published Online: 2005-06-01
Published in Print: 2002-01-23

Copyright © 2002 by Walter de Gruyter GmbH & Co. KG

Articles in the same Issue

  1. Non-Enzymatic Activities of Proteases: From Scepticism to Reality
  2. The Urokinase Plasminogen Activator Receptor in the Regulation of the Actin Cytoskeleton and Cell Motility
  3. The Molecular Basis for Anti-Proteolytic and Non-Proteolytic Functions of Plasminogen Activator Inhibitor Type-1: Roles of the Reactive Centre Loop, the Shutter Region, the Flexible Joint Region and the Small Serpin Fragment
  4. Nervous System Pathology: The Fibrin Perspective
  5. Post-Transcriptional Regulation of Gene Expression in the Plasminogen Activation System
  6. Role of Myofibroblasts at the Invasion Front
  7. Transmodulation of Cell Surface Regulatory Molecules via Ectodomain Shedding
  8. The Plasminogen Activating System in Periodontal Health and Disease
  9. Apolipoprotein(a): Structure-Function Relationship at the Lysine-Binding Site and Plasminogen Activator Cleavage Site
  10. Anti-Invasive Effects of Green Tea Polyphenol EpiGalloCatechin-3-Gallate (EGCG), a Natural Inhibitor of Metallo and Serine Proteases
  11. Inhibition of Receptor-Dependent Urokinase Signaling by Specific Ser to Glu Substitutions
  12. Activation of p38 MAP-Kinase and Caldesmon Phosphorylation Are Essential for Urokinase-Induced Human Smooth Muscle Cell Migration
  13. Growth Factor-Dependent Proliferation and Invasion of Muscle Satellite Cells Require the Cell-Associated Fibrinolytic System
  14. The Col-1 Module of Human Matrix Metalloproteinase-2 (MMP-2): Structural/Functional Relatedness between Gelatin-Binding Fibronectin Type II Modules and Lysine-Binding Kringle Domains
  15. Random Peptide Bacteriophage Display as a Probe for Urokinase Receptor Ligands
  16. Plasmin Produces an E-Cadherin Fragment That Stimulates Cancer Cell Invasion
  17. The Role of Proteases in Fibronectin Matrix Remodeling in Thyroid Epithelial Cell Monolayer Cultures
  18. Induction of Fibronectin mRNA by Urokinase- and Tissue-Type Plasminogen Activator in Human Skin Fibroblasts: Differential Role of u-PA and t-PA at the Fibronectin Protein Level
  19. Platelet Activating Factor Inhibits the Expression of Matrix Metalloproteinases and Affects Invasiveness and Differentiation in a System of Human Neuroblastoma Clones
  20. UVA Light Stimulates the Production of Cathepsin G and Elastase-Like Enzymes by Dermal Fibroblasts: A Possible Contribution to the Remodeling of Elastotic Areas in Sun-Damaged Skin
  21. uPA-Silica-Particles (SP-uPA): A Novel Analytical System to Investigate uPA-uPAR Interaction and to Test Synthetic uPAR Antagonists as Potential Cancer Therapeutics
  22. Monocyte-Expressed Urokinase Regulates Human Vascular Smooth Muscle Cell Migration in a Coculture Model
  23. Distinct Expression Pattern of Two Related Human Proteins Containing Multiple Types of Protease-Inhibitory Modules
  24. Osteopontin Modulates Prostate Carcinoma Invasive Capacity through RGD-Dependent Upregulation of Plasminogen Activators
  25. Expression of Matrix Metalloproteases (MMP-2, MT1-MMP) and Their Tissue Inhibitor (TIMP-2) by Rat Sertoli Cells in Culture: Implications for Spermatogenesis
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