Annexins in the regulation of proliferation
The understanding of the molecular mechanisms important in cellular proliferation during inflammatory, autoimmune and neoplastic disease is essential in the development of rational approaches to diagnosis and treatment. Therefore, it is critical to identify genes and proteins that could be dysregulated in these diseases. My lab is interested in the functions of a particular endogenous anti-inflammatory protein, annexin-1 (ANX-1).
ANX-1 , the first member of a growing super-family of calcium and phospholipids binding proteins has been shown to be involved in the anti-inflammatory actions of glucocorticoids, used widely in the clinical treatment of inflammatory diseases such as rheumatoid arthritis and asthma. In this regard, dysregulation of ANXA1 has been reported in a number of diseases, and differential expression of ANXA1 has been reported during the development and progression of cancer. Annexin-1 has roles in apoptosis, proliferation, and differentiation. However, the exact signaling mechanism through which annexin-1 exerts its functions is unknown. We are interested in studying the role that ANX-1 plays in the homeostatic regulation of cellular function, including proliferation. Our data suggests that ANX-1 may be involved in the regulation of leukocytic cell proliferation, as its expression spontaneously up-regulated upon thresholds of high density and low serum levels, correlating with lower proliferation rates. In this way, unstimulated cells may upregulate ANXA1 after crossing a threshold of cell density, and this regulation may be linked to the activation of p38 and ERK Map kinases.
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