Loss of KLF14 triggers centrosome amplification and tumorigenesis

Guangjian Fan, Lianhui Sun, Peipei Shan, Xianying Zhang, Jinliang Huan, Xiaohong Zhang, Dali Li, Tingting Wang, Tingting Wei, Xiaohong Zhang, Xiaoyang Gu, Liangfang Yao, Yang Xuan, Zhaoyuan Hou, Yongping Cui, Liu Cao, Xiaotao Li, Shengping Zhang () and Chuangui Wang ()
Additional contact information
Guangjian Fan: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University
Lianhui Sun: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University
Peipei Shan: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University
Xianying Zhang: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University
Jinliang Huan: Shanghai Eighth People’s Hospital
Xiaohong Zhang: USF Morsani College of Medicine
Dali Li: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University
Tingting Wang: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University
Tingting Wei: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University
Xiaohong Zhang: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University
Xiaoyang Gu: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University
Liangfang Yao: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University
Yang Xuan: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University
Zhaoyuan Hou: Shanghai Jiao Tong University School of Medicine
Yongping Cui: Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University
Liu Cao: Key Laboratory of Medical Cell Biology, College of Translational Medicine, China Medical University
Xiaotao Li: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University
Shengping Zhang: Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Chuangui Wang: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: Abstract Centrosome amplification is frequent in cancer, but the underlying mechanisms remain unclear. Here we report that disruption of the Kruppel-like factor 14 (KLF14) gene in mice causes centrosome amplification, aneuploidy and spontaneous tumorigenesis. Molecularly, KLF14 functions as a transcriptional repressor of Plk4, a polo-like kinase whose overexpression induces centrosome overduplication. Transient knockdown of KLF14 is sufficient to induce Plk4-directed centrosome amplification. Clinically, KLF14 transcription is significantly downregulated, whereas Plk4 transcription is upregulated in multiple types of cancers, and there exists an inverse correlation between KLF14 and Plk4 protein expression in human breast and colon cancers. Moreover, KLF14 depletion promotes AOM/DSS-induced colon tumorigenesis. Our findings reveal that KLF14 reduction serves as a mechanism leading to centrosome amplification and tumorigenesis. On the other hand, forced expression of KLF14 leads to mitotic catastrophe. Collectively, our findings identify KLF14 as a tumour suppressor and highlight its potential as biomarker and therapeutic target for cancer.

Date: 2015
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DOI: 10.1038/ncomms9450

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