Neoplastic transformation and the Epithelial-to-Mesenchymal Transition (EMT) are thought to lie at the opposite ends of cancer progression and be driven by distinct oncogenic alterations. Because they govern several aspects of epithelial adhesion and polarity, Rho GTPAses could function as tumor suppressors. By coupling DNA microarray analysis to genetic inactivation with RNAi, Tomoyo Okada has identified an atypical Rho family GTPase as a potential tumor suppressor in breast cancer. Interestingly, this GTPase appears to restrain Ras signaling and its inactivation simultaneously induces hyperproliferation and a full EMT. These results suggest that the inactivation of this GTPase may cause both tumor initiation and EMT, facilitating early dissemination in breast cancer. Ilaria Esposito is currently examining the molecular mechanism by which this GTPase suppresses activation of Ras.