Ras downstream effector GGCT alleviates oncogenic stress, represents a novel cancer-specific drug target

How cells adapt to oncogenic transformation associated cellular stress and become fully transformed is still unknown. Here we identified a novel GGCT regulated glutathione (GSH) - reactive oxygen species (ROS) metabolic pathway in oncogenic stress alleviation. We identified GGCT as a novel target of oncogenic Ras, and is required for oncogenic Ras induced primary mouse cell proliferation and transformation, and in vivo lung cancer formation in the LSL-Kras G12D mouse model. However, GGCT deficiency is compatible with normal mouse development, suggesting GGCT can be a cancer specific therapeutic target. Genetic amplified GGCT locus further supports the oncogenic driving function of GGCT. In summary, our study not only identifies a novel oncogenic function of GGCT, but also identifies a novel regulator of GSH metabolism, with implications for further understanding of oncogenic stress and cancer treatment.