Aurora B Inhibitor TAK-901 Synergizes with BCL-xL Inhibition by Inducing Active BAX in Cancer Cells
2017
Background:
Aurora B kinaseplays an essential role in
chromosome segregationand
cytokinesis, and is dysregulated in many cancer types, making it an attractive therapeutic target. TAK-901 is a potent aurora B inhibitor that showed efficacy in both in vitro and in vivo oncology models. Materials and Methods: We conducted a
synthetic lethalsiRNA screening to identify the genes that, when silenced, can potentiate the cell growth-inhibitory effect of TAK-901. Results: B-cell lymphoma-extra large (
BCL-xL) depletion by siRNA or chemical inhibition synergized with TAK-901 in cancer cell lines. As a mechanism of
synthetic lethality, active BCL2 associated X, apoptosis regulator (BAX) was induced by TAK-901.
BCL-xLprotected cells from BAX-dependent apoptosis induction. Therefore, TAK-901 sensitizes cancer cells to
BCL-xLinhibition. Conclusion:
Polyploidcells induced by TAK-901 are vulnerable to
BCL-xLinhibition. Our findings may have an impact on combination strategies with aurora B inhibitors in clinical studies.
Keywords:
-
Correction
-
Source
-
Cite
-
Save
0
References
7
Citations
NaN
KQI