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Abstract
BACKGROUND:
Although MASTL (microtubule-associated serine/threonine kinase-like) is a key mitotic kinase that regulates mitotic progression through the inactivation of tumor suppressor protein phosphatase 2A (PP2A), the antitumor mechanism of MASTL targeting in cancer cells is still unclear.

METHODS:
MASTL expression was evaluated by using breast cancer tissue microarrays and public cancer databases. The effects of MASTL depletion with siRNAs were evaluated in various breast cancer cells or normal cells. Various methods, including cell viability, cell cycle, soft agar, immunoblotting, immunofluorescence, PP2A activity, live image, and sphere forming assay, were used in this study.

RESULTS:
This study showed the oncosuppressive mechanism of MASTL targeting that promotes mitotic catastrophe through PP2A activation selectively in breast cancer cells. MASTL expression was closely associated with tumor progression and poor prognosis in breast cancer. The depletion of MASTL reduced the oncogenic properties of breast cancer cells with high MASTL expression, but did not affect the viability of non-transformed normal cells with low MASTL expression. With regard to the underlying mechanism, we found that MASTL inhibition caused mitotic catastrophe through PP2A activation in breast cancer cells. Furthermore, MASTL depletion enhanced the radiosensitivity of breast cancer cells with increased PP2A activity. Notably, MASTL depletion dramatically reduced the formation of radioresistant breast cancer stem cells in response to irradiation.

CONCLUSION:
Our data suggested that MASTL inhibition promoted mitotic catastrophe through PP2A activation, which led to the inhibition of cancer cell growth and a reversal of radioresistance in breast cancer cells.

Author information

Yoon YN1,2, Choe MH1,3, Jung KY4, Hwang SG1, Oh JS5, Kim JS6,7.
1
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-Dong, Nowon-Ku, Seoul, 139-706, South Korea.
2
Radiological and Medico-Oncological Sciences, University of Science and Technology, Daejeon, South Korea.
3
Department of Life Sciences and Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul, South Korea.
4
Center for Medicinal Chemistry, Korea Research Institute of Chemical Technology, Daejeon, South Korea.
5
Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, South Korea. ohjs@skku.edu.
6
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-Dong, Nowon-Ku, Seoul, 139-706, South Korea. jaesung@kirams.re.kr.
7
Radiological and Medico-Oncological Sciences, University of Science and Technology, Daejeon, South Korea. jaesung@kirams.re.kr.