The vast majority of cancer morbidity and mortality arises from tumor progression beyond the primary tumor site. Unfortunately, most therapies are not effective for advanced stage disease with regional extension or distant metastases. Thus, new treatments are needed to target rate limiting steps in tumor progression. The ability of cancers to invade and metastasize requires the acquisition of specific cell behaviors that enable the cell to escape from the localized site, breach the defined boundaries, reach a hospitable ectopic site and grow in this new locale. Recently, dysregulation of cell motility as stimulated by various extracellular factors has gained credence as a rate-limiting alteration in tumor progression in carcinomas and some other solid tumors. This has focused attention on initiators of signaling cascades that regulate tumor migration. In this effort, one molecule, phospholipase C-γ1 (PLCγ), has been shown to function as a key molecular switch.