Nuclear AURKA acquires kinase-independent transactivating function to enhance breast cancer stem cell phenotype

Feimeng Zheng, Caifeng Yue, Guohui Li, Bin He, Wei Cheng, Xi Wang, Min Yan, Zijie Long, Wanshou Qiu, Zhongyu Yuan, Jie Xu, Bing Liu, Qian Shi, Eric W.-F. Lam, Mien-Chie Hung and Quentin Liu ()
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Feimeng Zheng: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou
Caifeng Yue: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou
Guohui Li: State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences
Bin He: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou
Wei Cheng: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou
Xi Wang: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou
Min Yan: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou
Zijie Long: The Third Affiliated Hospital, Sun Yat-Sen University
Wanshou Qiu: The Third Affiliated Hospital, Sun Yat-Sen University
Zhongyu Yuan: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou
Jie Xu: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou
Bing Liu: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou
Qian Shi: Cancer Hospital/Cancer Institute, College of Life Sciences and Institutes of Biomedical Sciences, Fudan University
Eric W.-F. Lam: Imperial College London
Mien-Chie Hung: The University of Texas MD Anderson Cancer Center
Quentin Liu: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou

Nature Communications, 2016, vol. 7, issue 1, 1-17

Abstract: Abstract Centrosome-localized mitotic Aurora kinase A (AURKA) facilitates G2/M events. Here we show that AURKA translocates to the nucleus and causes distinct oncogenic properties in malignant cells by enhancing breast cancer stem cell (BCSC) phenotype. Unexpectedly, this function is independent of its kinase activity. Instead, AURKA preferentially interacts with heterogeneous nuclear ribonucleoprotein K (hnRNP K) in the nucleus and acts as a transcription factor in a complex that induces a shift in MYC promoter usage and activates the MYC promoter. Blocking AURKA nuclear localization inhibits this newly discovered transactivating function of AURKA, sensitizing resistant BCSC to kinase inhibition. These findings identify a previously unknown oncogenic property of the spatially deregulated AURKA in tumorigenesis and provide a potential therapeutic opportunity to overcome kinase inhibitor resistance.

Date: 2016
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DOI: 10.1038/ncomms10180

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