Figure 2.

Rho GTPase signaling can be deregulated in cancer by a wide range of mechanisms. (1) Evidence is emerging of many direct mutations of GTPases, such as the Rac1 P29S mutation which is a novel driver in melanoma. (2) GEFs are found overexpressed in many different cancer types, consistent with aberrant Rho GTPase signaling driving transformation and oncogenic progression. (3) Negative regulators of Rho GTPases, such as Rho GAPs and Rho GDIs, have been shown to be tumour suppressors, and lost in human cancers. (4) GTPases are often found to be overexpressed in human cancers, where they drive a variety of oncogenic processes. (5) Post-translational modifications of GTPases, such as changes in ubiquitylation or sumoylation, can alter their signaling. (6) The Rac1b splice form of Rac1 is found in multiple cancers including breast, colon and lung.