School of Life Science and Technology, ShanghaiTech University, Shanghai 201203, China; Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China
Shixiang Wang
School of Life Science and Technology, ShanghaiTech University, Shanghai 201203, China; Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China
Yuanyuan Shao
School of Life Science and Technology, ShanghaiTech University, Shanghai 201203, China
Jing Zhang
School of Life Science and Technology, ShanghaiTech University, Shanghai 201203, China; Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China
Xiaolin Wu
School of Life Science and Technology, ShanghaiTech University, Shanghai 201203, China
Yuxing Chen
School of Life Science and Technology, ShanghaiTech University, Shanghai 201203, China
Junhao Hu
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China
Feng Zhang
Core Facility, Department of Clinical Laboratory, Quzhou People's Hospital, Quzhou, Zhejiang, China
Xue-Song Liu
School of Life Science and Technology, ShanghaiTech University, Shanghai 201203, China; Corresponding author
Summary: 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 target of oncogenic Ras and that it 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 that GGCT can be a cancer-specific therapeutic target. Genetically amplified GGCT locus further supports the oncogenic driving function of GGCT. In summary, our study not only identifies an oncogenic function of GGCT but also identifies a novel regulator of GSH metabolism, with implications for further understanding of oncogenic stress and cancer treatment. : Biological Sciences; Cell Biology; Cancer Subject Areas: Biological Sciences, Cell Biology, Cancer
