MKI-1, a Novel Small-Molecule Inhibitor of MASTL, Exerts Antitumor and Radiosensitizer Activities Through PP2A Activation in Breast Cancer
Ah Young Kim, Yi Na Yoon, Jiyeon Leem, Jee‐Young Lee, Kwan‐Young Jung, Minsung Kang, Jiyeon Ahn, Sang‐Gu Hwang, Jeong Su Oh, Jae‐Sung Kim
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.