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

Author

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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
    Institute of Cancer Stem Cell, Dalian Medical University)

  • Caifeng Yue

    (Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou
    Institute of Cancer Stem Cell, Dalian Medical University
    The First Affiliated Hospital, Sun Yat-Sen University)

  • 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
    Institute of Cancer Stem Cell, Dalian Medical University)

  • Wei Cheng

    (Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou
    Institute of Cancer Stem Cell, Dalian Medical University)

  • Xi Wang

    (Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou
    Institute of Cancer Stem Cell, Dalian Medical University)

  • Min Yan

    (Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou
    Institute of Cancer Stem Cell, Dalian Medical University)

  • 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
    Institute of Cancer Stem Cell, Dalian Medical University)

  • Jie Xu

    (Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou
    Institute of Cancer Stem Cell, Dalian Medical University)

  • Bing Liu

    (Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou
    Institute of Cancer Stem Cell, Dalian Medical University)

  • 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
    Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University)

  • Quentin Liu

    (Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou
    Institute of Cancer Stem Cell, Dalian Medical University
    The Third Affiliated Hospital, Sun Yat-Sen University)

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.

Suggested Citation

  • 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 & Quentin Li, 2016. "Nuclear AURKA acquires kinase-independent transactivating function to enhance breast cancer stem cell phenotype," Nature Communications, Nature, vol. 7(1), pages 1-17, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10180
    DOI: 10.1038/ncomms10180
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    Cited by:

    1. Ming Shen Tham & Denny L. Cottle & Allara K. Zylberberg & Kieran M. Short & Lynelle K. Jones & Perkin Chan & Sarah E. Conduit & Jennifer M. Dyson & Christina A. Mitchell & Ian M. Smyth, 2024. "Deletion of Aurora kinase A prevents the development of polycystic kidney disease in mice," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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