The study of cancer cells in culture have led to the description of the "transformed phenotype" which alludes, in part, to the alterations in serum and adhesion dependent growth properties of cells. Furthermore, in malignant transformation there are changes in cell morphology, loss of contact inhibition and adherens junctions and increased cell migration. A vast majority of these changes have been attributed to alterations in the actin cytoskeleton. The small GTPases, Rho, Rac and CDC42, are believed to be responsible for the formation of actin mediated assemblies such as stress fibers, focal adhesions, lamellipodia and filipodia, while Rap1 is implicated in adherens junctions in both normal and transformed cells. However, the mechanism(s) responsible for loss of control of the small GTPases in cancer, however, is not clear. The primary reason is that many individual proteins in the large complex of proteins around actin mediated cytoskeletal structures still remain unidentified. The detailed description of these cytoskeletal protein networks will come by combining the power of genetics with proteomics, and will provide further insight into cancer progression and distant metastasis. This is the focus my laboratory investigation.