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Nat Commun. 2015 Oct 6;6:8450. doi: 10.1038/ncomms9450.

Loss of KLF14 triggers centrosome amplification and tumorigenesis.

Author information

1
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University, Shanghai 200241, China.
2
Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 650 Xinsongjiang Road, Songjiang District, Shanghai 201620, China.
3
Department of General Surgery, Shanghai Eighth People's Hospital, Shanghai 200235, China.
4
Department of Pathology and Cell Biology, USF Morsani College of Medicine, 12901 Bruce B. Downs Boulevard, Tampa, Florida 33612, USA.
5
Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
6
Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Shanxi 030001, China.
7
Key Laboratory of Medical Cell Biology, College of Translational Medicine, China Medical University, Shenyang 110000, China.

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.

PMID:
26439168
PMCID:
PMC4600754
DOI:
10.1038/ncomms9450
[Indexed for MEDLINE]
Free PMC Article

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