Report
Rapid proliferation of daughter cells lacking particular chromosomes due to multipolar mitosis promotes clonal evolution in colorectal cancer cells
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Volume 11, Issue 14 July 15, 2012
Pages 2650 - 2659
http://dx.doi.org/10.4161/cc.20976
Keywords: aneuploidy, cell cycle, chromosome instability, colorectal cancer cells, fluorescence in situ hybridization, long-term live cell imaging, multipolar mitosis
Authors: Chao Yang, Xiaoyun Shi, Yun Huang, Zhen Zhang, Howard J. Cooke, Mingrong Wang and Qinghua Shi
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- Chao Yang
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School of Life Sciences; University of Science and Technology of China; Hefei, Anhui, China; Current affiliation: College of Life Science; Anhui Normal University; Anhui, China
- Xiaoyun Shi
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School of Life Sciences; University of Science and Technology of China; Hefei, Anhui, China
- Yun Huang
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School of Life Sciences; University of Science and Technology of China; Hefei, Anhui, China
- Zhen Zhang
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School of Life Sciences; University of Science and Technology of China; Hefei, Anhui, China
- Howard J. Cooke
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School of Life Sciences; University of Science and Technology of China; Hefei, Anhui, China; MRC Human Genetics Unit and Institute of Genetics and Molecular Medicine; Western General Hospital; Edinburgh, UK
- Mingrong Wang
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State Key Laboratory of Molecular Oncology; Cancer Institute (Hospital); Peking Union Medical College and Chinese Academy of Medical Sciences; Beijing, China
- Qinghua Shi
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Corresponding author: qshi@ustc.edu.cn
School of Life Sciences; University of Science and Technology of China; Hefei, Anhui, China; Hefei National Laboratory for Physical Sciences at Microscale; Hefei, Anhui, China
Abstract:
Aneuploidy and chromosome instability (CIN) are hallmarks of the vast majority of solid tumors. However, the origins of aneuploid cells are unknown. The aim of this study is to improve our understanding of how aneuploidy and/or CIN arise and of karyotype evolution in cancer cells. By using fluorescence in situ hybridization (FISH) on cells after long-term live cell imaging, we demonstrated that most (> 90%) of the newly generated aneuploid cells resulted from multipolar divisions. Multipolar division occurred in mononucleated and binucleated parental cells, resulting in variation of chromosome compositions in daughter cells. These karyotypes can have the same chromosome number as their mother clone or lack a copy of certain chromosomes. Interestingly, daughter cells that lost a chromosome were observed to survive and form clones with shorter cell cycle duration. In our model of cancer cell evolution, the rapid proliferation of daughter cells from multipolar mitosis promotes colonal evolution in colorectal cancer cells.
Received: March 22, 2012; Accepted: June 1, 2012
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