Cell motility requires continuous reorganization of the actin cytoskeleton and is initiated by the formation of lamellipodia, while tumor cell invasion requires the formation of invadopodia. Production of these protrusive structures requires coordination regulation of the cortical actin network, a process regulated by a variety of actin-binding proteins. Our work is centered on the function of cortactin, an actin-binding protein and tyrosine kinase substrate, in the formation of lamellipodia, invadopodia and tumor cell invasion in vitro.

Cortactin interacts with F-actin and activates the Arp2/3 complex, a requirement for initiating actin polymerization-based membrane protrusion responsible for cell movement. By its ability to interact with a variety of adaptor proteins, cortactin serves to link transmembrane receptor complexes to the cortical actin cytoskeleton. Cortactin is also a substrate of Src and MAPK, two enzymes that play a central role in neoplastic transformation and cell movement. Overexpression of cortactin occurs in several carcinomas, most frequently in head and neck squamous cell carcinoma resulting from amplification of the chromosome 11q13 region. Cortactin gene amplification (CTTN) and protein overexpression in carcinomas is associated with poor patient outcome and increased metastatic disease.