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

作者：Fei-Meng Zheng, Caifeng Yue, Guohui Li, Bin He, Wei Cheng, Xi Wang, Min Yan, Zi‐Jie Long, Wanshou Qiu, Zhongyu Yuan, Jie Xu, Bing Liu, Qian Shi, Eric W.‐F. Lam, Mien‐Chie Hung, Quentin Liu · 发表于：Nature Communications · 年份：2016 · DOI：10.1038/ncomms10180 · 被引用次数：201 · 研究领域：Microtubule and mitosis dynamics、Gene Regulatory Network Analysis、Cancer-related Molecular Pathways

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.