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Loss of KLF14 triggers centrosome amplification and tumorigenesis

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  • Guangjian Fan

    (Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University
    Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine)

  • Lianhui Sun

    (Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University
    Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine)

  • Peipei Shan

    (Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University
    Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine)

  • 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
    Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
    Key Laboratory of Medical Cell Biology, College of Translational Medicine, China Medical University)

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.

Suggested Citation

  • 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 & Zhaoyu, 2015. "Loss of KLF14 triggers centrosome amplification and tumorigenesis," Nature Communications, Nature, vol. 6(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9450
    DOI: 10.1038/ncomms9450
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    Cited by:

    1. Lianhui Sun & Yuan Zhang & Boyu Yang & Sijun Sun & Pengshan Zhang & Zai Luo & Tingting Feng & Zelin Cui & Ting Zhu & Yuming Li & Zhengjun Qiu & Guangjian Fan & Chen Huang, 2023. "Lactylation of METTL16 promotes cuproptosis via m6A-modification on FDX1 mRNA in gastric cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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