A new role for cortactin in invadopodia: regulation of protease secretion.

Invadopodia are actin-dependent organelles that function in the invasion and remodeling of the extracellular matrix (ECM) by tumor cells. Cortactin, a regulator of the Arp2/3 complex, is of particular importance in invadopodia function. While most of the focus has been on the possible role of cortactin in actin assembly for direct formation of actin-rich invadopodia puncta, our recent data suggest that the primary role of cortactin in invadopodia is to promote protease secretion. In this manuscript, we review our previous work and present new data showing that cortactin is essential for both the localization of key invadopodia matrix metalloproteinases (MMPs) to actin-positive puncta at the cell-ECM interface and for ECM degradation induced by overexpression of MT1-MMP-GFP. Based on these data and results from the literature, we propose potential mechanisms by which cortactin may link vesicular trafficking and dynamic branched actin assembly to regulate protease secretion for invadopodia-associated ECM degradation.