Targeting human MutT homolog 1 (MTH1) in melanoma

This thesis examined the effect of the MTH1 inhibitor TH588 and MTH1 knockdown on melanoma cell survival and highlighted that the induction of apoptosis of melanoma cells by TH588 was mediated by ROS via activation of Bad and downregulation of Bcl-2 and Mcl-1. Moreover, studies reveal a novel function of Skp2 in protecting genomic integrity through MTH1 in melanoma cells under oxidative stress, and demonstrate that activation of the MAPK pathway protects melanoma cells from oxidative stress through the Skp2/MTH1 axis.