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

Nature Communications
Feimeng ZhengQuentin Liu

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.

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Datasets Mentioned

BETA
SAB4300603
GSE57931

Methods Mentioned

BETA
immunoprecipitation
co-immunoprecipitation
pull-down
fluorescence resonance
co-IP
ChIP
fluorescence-activated cell sorting
xenograft
xenografts
nuclear translocation

Software Mentioned

GSEA
SPSS
BioWorks
Gromacs4
Image pro plus
SILAC
TASSER

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