Ras Downstream Effector GGCT Alleviates Oncogenic Stress

• Published in: iScience Vol. 19; pp. 256 - 266
• Main Authors: He, Zaoke, Wang, Shixiang, Shao, Yuanyuan, Zhang, Jing, Wu, Xiaolin, Chen, Yuxing, Hu, Junhao, Zhang, Feng, Liu, Xue-Song
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.09.2019; Elsevier
• Subjects: Biological Sciences; Cancer; Cell Biology; Biological Sciences; Cell Biology; Cancer
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2019.07.036

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. [Display omitted] •GGCT is a target of Ras and is required for Ras-induced cancer formation•GGCT deletion is compatible with normal mouse development and tissue function•GGCT genomic locus is amplified in multiple human cancer types•GGCT could alleviate oncogenic stress by regulating GSH-ROS metabolism Biological Sciences; Cell Biology; Cancer