Abstract P1-08-09: Aurora kinase-A protein stability is negatively regulated by eEF1α2 and PTEN in breast cancer: Prognostic and therapeutic implications

Background: The AURKA gene encoding Aurora kinase-A (Aurora-A) protein is localized on chromosome 20q13 that is frequently amplified and overexpressed across multiple cancer types correlating with patient prognosis. Aurora-A plays a pivotal role in faithful segregation of chromosomes and normal progression of mitosis, peaking at G2/M followed by degradation at the end of mitosis by APC/C (Cdh1). However, regulation of Aurora-A protein stability in human cancer cells is not well elucidated. Here, we show that Aurora-A is targeted for ubiquitination and degradation by SCF complex involving eEF1α2 and PTEN in human breast cancer cells. Methods: Using a panel of breast cancer cell lines, as in vitro models, the eEF1α2 was knocked down or ectopically expressed to test the stability of Aurora-A protein. For in vivo models, tissue micro arrays of human breast cancer were immunostained for Aurora-A and eEF1α2 expression and categorized values were statistically tested by Chi-squared test. In addition, the public breast cancer dataset (Transbig) was used to predict breast cancer prognosis by Kaplan-Meier survival analysis. Results: In breast cancer cell lines and patient samples, an eEF1α2 non-expressing group showed a trend of higher Aurora-A expression than eEF1α2 expressing group, whose trend was significant in patient samples (P Citation Format: Treekitkarnmongkol W, Kai K, Katayama H, Tian W, Rodriguez-Canales J, Sahin AA, Sen S. Aurora kinase-A protein stability is negatively regulated by eEF1α2 and PTEN in breast cancer: Prognostic and therapeutic implications [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-08-09.