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

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.

SUBMITTER: Kim AY

PROVIDER: S-EPMC7550800 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Kim Ah-Young AY Yoon Yi Na YN Leem Jiyeon J Lee Jee-Young JY Jung Kwan-Young KY Kang Minsung M Ahn Jiyeon J Hwang Sang-Gu SG Oh Jeong Su JS Kim Jae-Sung JS

Frontiers in oncology 20200929

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 ...[more]

PMID: 33117702

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Dataset Information

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

Publications

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

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