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Journal of Biomedicine and Biotechnology
Volume 2012 (2012), Article ID 353687, 21 pages
http://dx.doi.org/10.1155/2012/353687
Review Article

The Biochemistry and Regulation of S100A10: A Multifunctional Plasminogen Receptor Involved in Oncogenesis

1Centro de Biomedicina Molecular e Estrutural, University of Algarve, Campus of Gambelas, FCT Bld. 8, 8005-139 Faro, Portugal
2Department of Biochemistry & Molecular Biology, Dalhousie University, P.O. Box 1500, Halifax, NS, Canada B3H 4R2
3Department of Pathology, Dalhousie University, P.O. Box 1500, Halifax, NS, Canada B3H 4R2

Received 9 April 2012; Accepted 1 June 2012

Academic Editor: Lindsey A. Miles

Copyright © 2012 Patricia A. Madureira et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The plasminogen receptors mediate the production and localization to the cell surface of the broad spectrum proteinase, plasmin. S100A10 is a key regulator of cellular plasmin production and may account for as much as 50% of cellular plasmin generation. In parallel to plasminogen, the plasminogen-binding site on S100A10 is highly conserved from mammals to fish. S100A10 is constitutively expressed in many cells and is also induced by many diverse factors and physiological stimuli including dexamethasone, epidermal growth factor, transforming growth factor-α, interferon-γ, nerve growth factor, keratinocyte growth factor, retinoic acid, and thrombin. Therefore, S100A10 is utilized by cells to regulate plasmin proteolytic activity in response to a wide diversity of physiological stimuli. The expression of the oncogenes, PML-RARα and KRas, also stimulates the levels of S100A10, suggesting a role for S100A10 in pathophysiological processes such as in the oncogenic-mediated increases in plasmin production. The S100A10-null mouse model system has established the critical role that S100A10 plays as a regulator of fibrinolysis and oncogenesis. S100A10 plays two major roles in oncogenesis, first as a regulator of cancer cell invasion and metastasis and secondly as a regulator of the recruitment of tumor-associated cells, such as macrophages, to the tumor site.