SUMO-specific protease 6 promotes gastric cancer cell growth via deSUMOylation of FoxM1.

Abstract

SUMOylation is a post-translational modification exerted various effects on the target proteins. SUMOylation is a highly dynamic and reversible process, which has been shown to play an important role in tumorigenesis. However, the roles of sentrin/SUMO-specific proteases (SENPs), which mediate the reverse process of SUMOylation, in tumorigenesis remains largely unexplored. Here, we uncover a critical role of SENP6 in promoting gastric cancer cells growth via regulating the deSUMOylation of a transcription factor forkhead box protein M1 (FoxM1). We demonstrated that the mRNA and protein levels were elevated in gastric cancer tissues. Overexpression of SENP6 promoted, while RNA interference depletion of endogenous SENP6 inhibited gastric cancer cells growth and the ability of colony formation. By using biochemical assays, we identified FoxM1 as a novel substrate of SENP6 in gastric cancer cells. Thus, our data suggest that SENP6, which is highly expressed in gastric cancer cells, regulates the transcriptional activity and stability of FoxM1 through deSUMOylation.