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Ras Downstream Effector GGCT Alleviates Oncogenic Stress.


ABSTRACT: 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.

SUBMITTER: He Z 

PROVIDER: S-EPMC6700472 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Ras Downstream Effector GGCT Alleviates Oncogenic Stress.

He Zaoke Z   Wang Shixiang S   Shao Yuanyuan Y   Zhang Jing J   Wu Xiaolin X   Chen Yuxing Y   Hu Junhao J   Zhang Feng F   Liu Xue-Song XS  

iScience 20190726


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 deficienc  ...[more]

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