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Journal of Biomedicine and Biotechnology
Volume 2012 (2012), Article ID 406273, 13 pages
http://dx.doi.org/10.1155/2012/406273
Review Article

The Annexin A2/S100A10 System in Health and Disease: Emerging Paradigms

1Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA
2Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA
3Department of Pharmacology, Yale School of Medicine, New Haven, CT 06520, USA
4Department of Hematology, National Cancer Institute, Mexico City, Mexico
5Department of Pathology, Stony Brook University, Stony Brook, NY 11794, USA
6Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA
7Department of Pathology and Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA

Received 28 March 2012; Accepted 15 May 2012

Academic Editor: Lindsey A. Miles

Copyright © 2012 Nadia Hedhli 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

Since its discovery as a src kinase substrate more than three decades ago, appreciation for the physiologic functions of annexin A2 and its associated proteins has increased dramatically. With its binding partner S100A10 (p11), A2 forms a cell surface complex that regulates generation of the primary fibrinolytic protease, plasmin, and is dynamically regulated in settings of hemostasis and thrombosis. In addition, the complex is transcriptionally upregulated in hypoxia and promotes pathologic neoangiogenesis in the tissues such as the retina. Dysregulation of both A2 and p11 has been reported in examples of rodent and human cancer. Intracellularly, A2 plays a critical role in endosomal repair in postarthroplastic osteolysis, and intracellular p11 regulates serotonin receptor activity in psychiatric mood disorders. In human studies, the A2 system contributes to the coagulopathy of acute promyelocytic leukemia, and is a target of high-titer autoantibodies in patients with antiphospholipid syndrome, cerebral thrombosis, and possibly preeclampsia. Polymorphisms in the human ANXA2 gene have been associated with stroke and avascular osteonecrosis of bone, two severe complications of sickle cell disease. Together, these new findings suggest that manipulation of the annexin A2/S100A10 system may offer promising new avenues for treatment of a spectrum of human disorders.