Cell Surface Remodeling by Plasmin: A New Function for an Old Enzyme
Open Access
- 14 October 2012
- journal article
- review article
- Published by Hindawi Limited in Journal of Biomedicine and Biotechnology
- Vol. 2012, 1-21
- https://doi.org/10.1155/2012/564259
Abstract
Plasmin, one of the most potent and reactive serine proteases, is involved in various physiological processes, including embryo development, thrombolysis, wound healing and cancer progression. The proteolytic activity of plasmin is tightly regulated through activation of its precursor, plasminogen, only at specific times and in defined locales as well as through inhibition of active plasmin by its abundant natural inhibitors. By exploiting the plasminogen activating system and overexpressing distinct components of the plasminogen activation cascade, such as pro-uPA, uPAR and plasminogen receptors, malignant cells can enhance the generation of plasmin which in turn, modifies the tumor microenvironment to sustain cancer progression. While plasmin-mediated degradation and modification of extracellular matrix proteins, release of growth factors and cytokines from the stroma as well as activation of several matrix metalloproteinase zymogens, all have been a focus of cancer research studies for decades, the ability of plasmin to cleave transmembrane molecules and thereby to generate functionally important cleaved products which induce outside-in signal transduction, has just begun to receive sufficient attention. Herein, we highlight this relatively understudied, but important function of the plasmin enzyme as it is generatedde novoat the interface between cross-talking cancer and host cells.Keywords
This publication has 146 references indexed in Scilit:
- VEGF-A and Tenascin-C produced by S100A4 + stromal cells are important for metastatic colonizationProceedings of the National Academy of Sciences of the United States of America, 2011
- The Role of Annexin A2 in Tumorigenesis and Cancer ProgressionCancer Microenvironment, 2011
- VHL loss in renal cell carcinoma leads to up-regulation of CUB domain-containing protein 1 to stimulate PKCδ-driven migrationProceedings of the National Academy of Sciences of the United States of America, 2011
- CUB-domain–containing protein 1 (CDCP1) activates Src to promote melanoma metastasisProceedings of the National Academy of Sciences of the United States of America, 2011
- Proteolysis-induced N-terminal Ectodomain Shedding of the Integral Membrane Glycoprotein CUB Domain-containing Protein 1 (CDCP1) Is Accompanied by Tyrosine Phosphorylation of Its C-terminal Domain and Recruitment of Src and PKCδJournal of Biological Chemistry, 2010
- Plasmin-Mediated Degradation of Laminin γ-1 Is Critical for Ethanol-Induced NeurodegenerationBiological Psychiatry, 2009
- Neutrophil MMP-9 Proenzyme, Unencumbered by TIMP-1, Undergoes Efficient Activation in Vivo and Catalytically Induces Angiogenesis via a Basic Fibroblast Growth Factor (FGF-2)/FGFR-2 PathwayJournal of Biological Chemistry, 2009
- The Plasminogen Fibrinolytic Pathway Is Required for Hematopoietic RegenerationCell Stem Cell, 2007
- Plasminogen activation independent of uPA and tPA maintains wound healing in gene-deficient miceThe EMBO Journal, 2006
- Downregulation of uPA, uPAR and MMP-9 using small, interfering, hairpin RNA (siRNA) inhibits glioma cell invasion, angiogenesis and tumor growthNeuron Glia Biology, 2004