Mena, a phosphoprotein that regulates actin dynamics in lamellipodia of migratory cells, and PTEN, a phosphatase involved in signal transduction, are two proteins that have been implicated in human cancer cell motility and chemotaxis. A variant of Mena (Mena⁺⁺⁺) is expressed in an invasive subpopulation of mammary cancer cells that exhibit robust chemotaxis to epidermal growth factor (EGF). These observations have led to the hypothesis that EGF recruits carcinoma cells expressing the highly invasive Mena isoform into blood vessels, leading to metastasis. However, given the large distances that metastatic cells must travel within the human body, it is unlikely that the EGF chemotactic signal could be propagated by simple diffusion. Therefore, we are testing if Mena⁺⁺⁺ cells, like those of the model organism Dictyostelium discoideum, respond to waves of chemoattractant. In this scenario, effective concentrations of chemoattractant are propagated over long distances by a relay mechanism. Similarly, mutations in PTEN, a tumor suppressor protein, correlate with alterations in motility. However, it was recently shown that although pten- cells in D. discoideum exhibit defects in basic cell motility, they can still chemotax, albeit with diminished efficiency. These results raised the possibility that PTEN is not absolutely required for chemotaxis. To further examine the role of PTEN in signal transduction, we identified and cloned a pten- like gene in Dictyostelium. We can now measure the basic motility of cells lacking the PTEN-like protein in both normal and pten^- backgrounds.