Examining the Effect of Tks5 Sh3 Domain Mutations on Invadopodia Localization and Development in Cancer Cells

Metastasis, the process by which cancers spread from their site of origin to distant anatomic sites, accounts for about ninety percent of all cancer deaths. Metastasis occurs when cancer cells acquire the invasive behaviors necessary for breaching tissue boundaries. Invadopodia, actin-rich cell surface protrusions, stimulate metastasis by enabling adhesion, motility, and extracellular matrix remodeling by cancer cells. Src tyrosine kinase and its substrate Tks5 localize to invadopodia and regulate their development. Tks5 is composed of a PX domain followed by five SH3 domains. While the lipid-binding PX domain is essential for Tks5 dependent invadopodia localization and development, the five protein-binding SH3 domains of Tks5 are less defined.