RHOA L57V

Having previously characterized the Y42C RHOA mutation in gastric cancer, in this issue of Science Signaling, Schaefer et al. take on the slightly less common L57V mutation and find that individual RHOA mutations can have different and unpredictable signaling outcomes.

Both RHOA mutants stimulated the transcriptional co-activator YAP1 through actin dynamics to promote DGC progression; however, RHOA additionally did so by activating the kinases IGF1R and PAK1, distinct from the FAK-mediated mechanism induced by RHOA. Our results reveal that RHOA and RHOA drive the development of DGC through distinct biochemical and signaling mechanisms.