Rho GTPases in Transformation and Metastasis

During the development and progression of human cancer, cells undergo numerous changes in morphology, proliferation, and transcriptional profile. Over the past couple of decades there have been intense efforts to understand the molecular mechanisms involved, and members of the Ras superfamily of small GTPases have emerged as important players. Mutated versions of the Ras genes were first identified in human cancers some 20 years ago, but more recently, the Rho branch of the family has been receiving increased attention. In addition to the experimental evidence implicating Rho GTPase signaling in promoting malignant transformation, genetic analysis of human cancers has now revealed a few examples of direct alterations in the genes encoding regulators of Rho GTPases. In this review, we discuss the evidence implicating Rho GTPases in transformation and metastasis, as well as the progress made toward identifying their biochemical mechanism of action.