A mitotic NADPH upsurge promotes chromosome segregation and tumour progression in aneuploid cancer cells
A mitotic NADPH upsurge promotes chromosome segregation and tumour progression in aneuploid cancer cells
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DOI：
10.1038/s42255-023-00832-9
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发表时间：
2023
影响因子：
20.8
通讯作者：
Zhenye Yang
中科院分区：
文献类型：
--
作者：
Aoxing Cheng;Tian Xu;Weiyi You;Ting Wang;Dongming Zhang;Huimin Guo;Haiyan Zhang;Xin Pan;Yucai Wang;Liu Liu;Kaiguang Zhang;Jue Shi;Xuebiao Yao;Jing Guo;Zhenye Yang
Redox metabolites have been observed to fluctuate through the cell cycle in cancer cells, but the functional impacts of such metabolic oscillations remain unknown. Here, we uncover a mitosis-specific nicotinamide adenine dinucleotide phosphate (NADPH) upsurge that is essential for tumour progression. Specifically, NADPH is produced by glucose 6-phosphate dehydrogenase (G6PD) upon mitotic entry, which neutralizes elevated reactive oxygen species (ROS) and prevents ROS-mediated inactivation of mitotic kinases and chromosome missegregation. Mitotic activation of G6PD depends on the phosphorylation of its co-chaperone protein BAG3 at threonine 285, which results in dissociation of inhibitory BAG3. Blocking BAG3T285 phosphorylation induces tumour suppression. A mitotic NADPH upsurge is present in aneuploid cancer cells with high levels of ROS, while nearly unobservable in near-diploid cancer cells. High.BAG3T285 phosphorylation is associated with worse prognosis in a cohort of patients with microsatellite-stable colorectal cancer. Our study reveals that.aneuploid cancer cells with high levels of ROS depend on a G6PD-mediated NADPH upsurge in mitosis to protect them from ROS-induced chromosome.missegregation.
