Nuclear AURKA acquires kinase-independent transactivating function to enhance breast cancer stem cell phenotype.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26782714.
- Also identified by DOI 10.1038/ncomms10180 and PMC identifier 4735655.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Aurora Kinase A
- Breast Neoplasms
- Cell Nucleus
- Neoplastic Stem Cells