The Role of Actin Polymerization in Tumor Metastasis
Annual rept. 1 Aug 2001-31 Jul 2002
AMERICAN NATIONAL RED CROSS WASHINGTON DC
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Breast cancer is often accomplished with gene amplification of the chromosome 11q13, including EMS1 or cortactin, whose gene product is featured by a repeated domain and a SH3 domain at its C-terminus. Our recent study has demonstrated that overexpression of cortactin can promote metastasis based on an animal model in a tyrosine phosphorylation dependent manner. We also demonstrated that the primary biochemical function of cortactin is to activate Arp23 complex for the formation of a branched actin network at the cell front edge and to promote cell migration and invasion A cortactin mutant with deletion of the Arp23 binding domain resulted in decrease in cell motility and disturbance of actin polymerization at cell edges. Since actin dynamics is also known to be regulated by phospholipids, we examined the possibility for the regulation of cortactin by phosphatidylinositides. By a direct binding assay, we demonstrated that recombinant cortactin binds specifically to a subset of phosphatidylinositides. Current work is to determine the structural domain of cortactin that is responsible for the binding and the effect of the binding on the activity of cortactin.
- Anatomy and Physiology
- Medicine and Medical Research