MKI-1，一种新型的MASTL小分子抑制剂，通过激活PP2A在乳腺癌中发挥抗肿瘤和放射增敏活性。

MKI-1, a Novel Small-Molecule Inhibitor of MASTL, Exerts Antitumor and Radiosensitizer Activities Through PP2A Activation in Breast Cancer.

作者信息

Kim Ah-Young, Yoon Yi Na, Leem Jiyeon, Lee Jee-Young, Jung Kwan-Young, Kang Minsung, Ahn Jiyeon, Hwang Sang-Gu, Oh Jeong Su, Kim Jae-Sung

机构信息

Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.

Radiological and Medico-Oncological Sciences, University of Science and Technology, Daejeon, South Korea.

出版信息

Front Oncol. 2020 Sep 29;10:571601. doi: 10.3389/fonc.2020.571601. eCollection 2020.

Although MASTL (microtubule-associated serine/threonine kinase-like) is an attractive target for anticancer treatment, MASTL inhibitors with antitumor activity have not yet been reported. In this study, we have presented a novel MASTL inhibitor, MKI-1, identified through screening and analysis. Our data revealed that MKI-1 exerted antitumor and radiosensitizer activities in and models of breast cancer. The mechanism of action of MKI-1 occurred through an increase in PP2A activity, which subsequently decreased the c-Myc protein content in breast cancer cells. Moreover, the activity of MKI-1 in the regulation of MASTL-PP2A was validated in a mouse oocyte model. Our results have demonstrated a new small-molecule inhibitor of MASTL, MKI-1, which exerts antitumor and radiosensitizer activities through PP2A activation in breast cancer and

尽管微管相关丝氨酸/苏氨酸激酶样蛋白（MASTL）是抗癌治疗的一个有吸引力的靶点，但尚未有具有抗肿瘤活性的MASTL抑制剂的报道。在本研究中，我们展示了一种通过筛选和分析鉴定出的新型MASTL抑制剂MKI-1。我们的数据显示，MKI-1在乳腺癌的体内和体外模型中发挥抗肿瘤和放射增敏活性。MKI-1的作用机制是通过增加PP2A活性，进而降低乳腺癌细胞中的c-Myc蛋白含量。此外，在小鼠卵母细胞模型中验证了MKI-1在调节MASTL-PP2A方面的活性。我们的结果证明了一种新的MASTL小分子抑制剂MKI-1，它通过激活PP2A在乳腺癌体内和体外发挥抗肿瘤和放射增敏活性。