Abstract 3451: Depletion of Mastl kinase inhibits cancer growth by induction of mitotic catastrophe in breast cancer

Abstract

Abstract Targeting mitotic kinase is an emerging anticancer strategy with promising pre-clinical results. Mastl is an essential mitotic kinase regulating mitotic progression by inactivation of a tumor suppressor protein phosphatase 2A (PP2A). However, it is unclear whether inhibition of Mastl kinase can kills tumor cells. Here, we show that Mastl inhibition selectively kills cancer cells by induction of mitotic catastrophe in breast cancer cells. We found that Mastl overexpression was tightly associated with tumor progression and poor prognosis in breast cancer. Mastl depletion with specific siRNAs induced cell death in Mastl high breast cancer cells, but not in Mastl low breast cancer cells. Interestingly, Mastl depletion did not affect the viability of normal cells. In addition, Mastl depletion reduced the oncogenic properties of breast cancer cells. Furthermore, we found that Mastl depletion caused mitotic catastrophe. Therefore, our data indicate that inhibition of Mastl can selectively kill breast cancer cells by induction of mitotic catastrophe, providing that targeting Mastl kinase is a very useful approach for breast cancer treatment. Citation Format: Yoon Yina, Jae Sung Kim. Depletion of Mastl kinase inhibits cancer growth by induction of mitotic catastrophe in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3451. doi:10.1158/1538-7445.AM2017-3451