Aurora Kinase A and Bcl-xL Inhibition Suppresses Metastasis in Triple-Negative Breast Cancer.

Abstract

Triple-negative breast cancer (TNBC) is a heterogeneous disease that accounts for 10–15% of all breast cancer cases. Within TNBC, the treatment of basal B is the most challenging due to its highly invasive potential, and thus treatments to suppress metastasis formation in this subgroup are urgently needed. However, the mechanisms underlying the metastatic ability of TNBC remain unclear. In the present study, we investigated the role of Aurora A and Bcl-xL in regulating basal B cell invasion. We found gene amplification and elevated protein expression in the basal B cells, which also showed increased invasiveness in vitro, compared to basal A cells. Chemical inhibition of Aurora A with alisertib and siRNA-mediated knockdown of BCL2L1 decreased the number of invading cells compared to non-treated cells in basal B cell lines. The analysis of the correlation between AURKA and BCL2L1 expression in TNBC and patient survival revealed significantly decreased relapse-free survival (n = 534, p = 0.012) and distant metastasis-free survival (n = 424, p = 0.017) in patients with primary tumors exhibiting a high combined expression of AURKA and BCL2L1. Together, our findings suggest that high levels of Aurora A and Bcl-xL promote metastasis, and inhibition of these proteins may suppress metastasis and improve patient survival in basal B TNBC.