RhoA can lead the way in tumor cell invasion and metastasis.
The Rho family of GTPases is well-established regulators of cell migration, and has been implicated in the process of tumor cell invasion and metastasis. The RhoA signaling pathway is strongly correlated with the ability of tumor cells to invade and successfully establish metastases. In this review, we begin by discussing the gene expression data correlating Rho expression with metastasis, and then discuss two emerging concepts that help explain the underlying mechanisms by which RhoA may promote tumor metastasis. First, the use of sophisticated biosensor probes has revealed that RhoA is active in membrane protrusions. Second, the RhoA pathway affects the invasive behavior of tumor cells by promoting invadopodia, amoeboid migration, and the plasticity of tumor cells to modulate their migratory properties. Thus, our view of the role of the RhoA pathway in metastasis is evolving to include a previously unappreciated function at the leading edge.