Cortactin in invadopodia formation

1821

Invadopodia are invasive foot processes used by cancer cells to degrade extracellular matrix and move through tissue barriers, that depend on src kinase signaling and branched actin assembly. Podosomes are analogous structures found in src kinase-transformed cells that are molecularly and functionally similar to invadopodia. We studied the role of cortactin, a prominent invadopodia component, actin assembly molecule and src kinase substrate in cancer cell invasion and invadopodia formation. We found that cortactin promotes cancer cell invasion, through a domain that includes the src kinase phosphorylation sites and SH3 domain. To address the role of cortactin specifically in src-kinase-induced invadopodia/podosome formation, we knocked down cortactin in src-kinase transformed mouse embryonic fibroblasts. We found that cortactin knockdown inhibited podosome ring formation and matrix degradation in a time-dependent manner. We hypothesize that enhanced invadopodia formation may account for the aggressive behavior of cancers with amplifications in the cortactin/EMS1 gene.