In pancreatic ductal adenocarcinoma cells that retain TGFβ signaling, RAC1 regulates SMAD2 and SMAD3 at the post-transcriptional level, shifting TGFβ from a tumor-suppressive role to a tumor-promoting role (Ungefroren et al., 2011), suggesting that the relationship between the TGFβ and RHO/RAC GTPase pathways is complex and context-dependent but nevertheless central. The gene discussed is SMAD2; the disease is pancreatic ductal adenocarcinoma.