AUTHOR=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 TITLE=MKI-1, a Novel Small-Molecule Inhibitor of MASTL, Exerts Antitumor and Radiosensitizer Activities Through PP2A Activation in Breast Cancer JOURNAL=Frontiers in Oncology VOLUME=10 YEAR=2020 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.571601 DOI=10.3389/fonc.2020.571601 ISSN=2234-943X ABSTRACT=

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 in silico screening and in vitro analysis. Our data revealed that MKI-1 exerted antitumor and radiosensitizer activities in in vitro and in vivo 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 in vitro and in vivo.