Merck

Loss of KLF14 triggers centrosome amplification and tumorigenesis.

Nature communications (2015-10-07)
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, Chuangui Wang
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.

MATERIALS
Product Number
Brand
Product Description

Supelco
Cholesterol solution, certified reference material, 10 mg/mL in chloroform
Sigma-Aldrich
Cholesterol, from sheep wool, ≥92.5% (GC), powder
Sigma-Aldrich
Cholesterol, Sigma Grade, ≥99%
Sigma-Aldrich
Cholesterol, powder, BioReagent, suitable for cell culture, ≥99%
Sigma-Aldrich
SyntheChol® NS0 Supplement, 500 ×, synthetic cholesterol, animal component-free, sterile-filtered, aqueous solution, suitable for cell culture
SAFC
Cholesterol, from sheep wool, Controlled origin, meets USP/NF testing specifications
Sigma-Aldrich
Caffeine, SAJ special grade, ≥98.5%
Sigma-Aldrich
Caffeine, meets USP testing specifications, anhydrous
Sigma-Aldrich
Caffeine, Sigma Reference Standard, vial of 250 mg
Sigma-Aldrich
Caffeine, BioXtra
Sigma-Aldrich
ANTI-KLF14 (C-TERM) antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
Sigma-Aldrich
Caffeine, powder, ReagentPlus®
Sigma-Aldrich
Adenosine 5′-diphosphoribose sodium salt, ≥93%
Sigma-Aldrich
Caffeine, anhydrous, 99%, FCC, FG
SAFC
Cholesterol, Plant-Derived, SyntheChol®, NF, Ph. Eur., JP