Institute of Computing Technology, Chinese Academy IR
| Energy restriction causes metaphase delay and chromosome mis-segregation in cancer cells | |
| Cheng, Aoxing1,2; Jiang, Ya2; Wang, Ting2; Yu, Fazhi2; Ishrat, Iqra2; Zhang, Dongming2; Ji, Xiaoyang3,4,5; Chen, Minhua2; Xiao, Weihua1,2; Li, Qing1; Zhang, Kaiguang1; Niu, Gang3,4,5,6; Shi, Jue7,8; Pan, Yueyin1; Yang, Zhenye1,2,9; Guo, Jing1 | |
| 2021-05-30 | |
| 发表期刊 | CELL CYCLE
 |
| ISSN | 1538-4101 |
| 页码 | 14 |
| 摘要 | ATP metabolism during mitosis needs to be coordinated with numerous energy-demanding activities, especially in cancer cells whose metabolic pathways are reprogramed to sustain rapid proliferation in a nutrient-deficient environment. Although strategies targeting the energy metabolic pathways have shown therapeutic efficacy in preclinical cancer models, how normal cells and cancer cells differentially respond to energy shortage is unclear. In this study, using time-lapse microscopy, we found that cancer cells displayed unique mitotic phenotypes in a dose-dependent manner upon decreasing ATP (i.e. energy) supply. When reduction in ATP concentration was moderate, chromosome movements in mitosis were barely affected, while the metaphase-anaphase transition was significantly prolonged due to reduced tension between the sister-kinetochores, which delayed the satisfaction of the spindle assembly checkpoint. Further reduction in ATP concentration led to a decreased level of Aurora-B at the centromere, resulting in increased chromosome mis-segregation after metaphase delay. In contrast to cancer cells, ATP restriction in non-transformed cells induced cell cycle arrest in interphase, rather than causing mitotic defects. In addition, data mining of cancer patient database showed a correlation between signatures of energy production and chromosomal instability possibly resulted from mitotic defects. Together, these results reveal that energy restriction induces differential responses in normal and cancer cells, with chromosome mis-segregation only observed in cancer cells. This points to targeting energy metabolism as a potentially cancer-selective therapeutic strategy. |
| 关键词 | ATP energy restriction cancer cells metaphase-anaphase transition chromosome mis-segregation |
| DOI | 10.1080/15384101.2021.1930679 |
| 收录类别 | SCI |
| 语种 | 英语 |
| 资助项目 | National Natural Science Foundation of China[31701178] ; National Natural Science Foundation of China[31970670] ; National Natural Science Foundation of China[31771498] ; National Natural Science Foundation of China[92057104] ; National Natural Science Foundation of China[32000528] ; National Natural Science Foundation of China[32000492] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB19000000] ; Collaborative Innovation Program of Hefei Science Center[CAS 2019HSC-CIP011] ; Hefei National Laboratory for Physical Sciences at the Microscale[KF2020009] ; Open Project of the CAS Key Laboratory of Innate Immunity and Chronic Disease ; Fundamental Research Funds for the Central Universities |
| WOS研究方向 | Cell Biology |
| WOS类目 | Cell Biology |
| WOS记录号 | WOS:000655827200001 |
| 出版者 | TAYLOR & FRANCIS INC |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://119.78.100.204/handle/2XEOYT63/17580 |
| 专题 | 中国科学院计算技术研究所期刊论文_英文 |
| 通讯作者 | Pan, Yueyin; Yang, Zhenye; Guo, Jing |
| 作者单位 | 1.Univ Sci & Technol China, Div Life Sci & Med, USTC, Affiliated Hosp 1, Hefei, Peoples R China 2.Univ Sci & Technol China, Div Life Sci & Med, Sch Basic Med Sci, Hefei Natl Lab Phys Sci Microscale,CAS Key Lab In, Hefei, Peoples R China 3.Phil Rivers Technol Ltd, Joint Turing Darwin Lab, Beijing, Peoples R China 4.Chinese Acad Sci, Inst Comp Technol, Beijing, Peoples R China 5.Phil Rivers Technol Ltd, Dept Computat Biol, Beijing, Peoples R China 6.Chinese Acad Sci, West Inst Comp Technol, Chongqing, Peoples R China 7.Hong Kong Baptist Univ, Dept Phys, Ctr Quantitat Syst Biol, Hong Kong, Peoples R China 8.Hong Kong Baptist Univ, Dept Biol, Hong Kong, Peoples R China 9.Univ Sci & Technol China, Hefei, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cheng, Aoxing,Jiang, Ya,Wang, Ting,et al. Energy restriction causes metaphase delay and chromosome mis-segregation in cancer cells[J]. CELL CYCLE,2021:14. |
| APA | Cheng, Aoxing.,Jiang, Ya.,Wang, Ting.,Yu, Fazhi.,Ishrat, Iqra.,...&Guo, Jing.(2021).Energy restriction causes metaphase delay and chromosome mis-segregation in cancer cells.CELL CYCLE,14. |
| MLA | Cheng, Aoxing,et al."Energy restriction causes metaphase delay and chromosome mis-segregation in cancer cells".CELL CYCLE (2021):14. |
| 条目包含的文件 | 条目无相关文件。 | |||||
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