Signal transduction cascades initiated by growth factors and extracellular matrix-integrin interactions regulate cell adhesion and migration, cell growth and differentiation, and cancer cell growth and metastasis. Ongoing efforts focus on the role of focal adhesion kinase (FAK) in mediating signals from the extracellular matrix through integrin receptors. FAK and its interacting partners play a central role in propagating signals that regulate cell motility. Using “real time” imaging models coupled with biochemical analysis of adhesion signaling pathways, we are studying the role of FAK and adhesion signaling pathways in important and interesting cellular processes, including development, vascular function and cancer. A second area focuses on the novel actin binding protein, Cortactin. Cortactin regulates actin-dependent mechanisms important for membrane ruffling, endocytosis and cell motility. Cortactin binds to and regulates the Arp2/3 complex, a multi-protein complex that regulates filopodia and lamellipodia formation by promoting “branched actin polymerization”. Cortactin also binds to cell surface receptor complexes, targeting these complexes to sites of dynamic actin rearrangement. Finally, we are developing novel approaches to both define and eventually exploit, inhibitors of adhesion signaling as potential therapeutic drugs for prostate cancer metastasis.