Rho GTPases in human carcinogenesis: a tale of excess

Rho GTPases are proteins that in response to diverse stimuli control key signaling and structural aspects of the cell. Although early studies had proposed a role for Rho GTPases in cellular transformation, this effect was underestimated by the fact that no genetic mutations affecting Rho-encoding genes was found in human tumors. However, in recent years a high incidence of overexpression of different members of the family of Rho GTPases in human tumors has been detected which is leading to a great interest in the cellular effects elicited by these oncoproteins. As well, the characterization of downstream effectors and upstream regulators of Rho GTPases provides crucial clues on the specific cellular effects that permit aberrant cellular growth and tumorigenesis. A direct link between the functions of some of these signaling elements and regulation of the cell cycle, cytoskeletal rearrangements and cell adhesion has been observed in distinct types of human tumors. Provided this information, a number of drugs that affect Rho signaling at different levels have been described with promisingin vivo antitumoral activity. In this review, the current evidence of dysregulation of Rho signaling in human tumors is assembled.