Oncotarget

Research Papers:

The Aurora kinase A inhibitor TC-A2317 disrupts mitotic progression and inhibits cancer cell proliferation

Yoo Hong Min, Wootae Kim and Ja-Eun Kim _

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Oncotarget. 2016; 7:84718-84735. https://doi.org/10.18632/oncotarget.12448

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Abstract

Yoo Hong Min1, Wootae Kim1, Ja-Eun Kim1,2

1Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 130-701, Republic of Korea

2Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea

Correspondence to:

Ja-Eun Kim, email: jekim@khu.ac.kr

Keywords: Aurora kinase A, TC-A2317, mitosis, spindle assembly checkpoint

Abbreviations: Spindle assembly checkpoint, SAC.

Received: June 06, 2016    Accepted: September 16, 2016    Published: October 04, 2016

ABSTRACT

Mitotic progression is crucial for the maintenance of chromosomal stability. A proper progression is ensured by the activities of multiple kinases. One of these enzymes, the serine/threonine kinase Aurora A, is required for proper mitosis through the regulation of centrosome and spindle assembly. In this study, we functionally characterized a newly developed Aurora kinase A inhibitor, TC-A2317. In human lung cancer cells, TC-A2317 slowed proliferation by causing aberrant formation of centrosome and microtubule spindles and prolonging the duration of mitosis. Abnormal mitotic progression led to accumulation of cells containing micronuclei or multinuclei. Furthermore, TC-A2317–treated cells underwent apoptosis, autophagy or senescence depending on cell type. In addition, TC-A2317 inactivated the spindle assembly checkpoint triggered by paclitaxel, thereby exacerbating mitotic catastrophe. Consistent with this, the expression level of Aurora A in tumors was inversely correlated with survival in lung cancer patients. Collectively, these data suggest that inhibition of Aurora kinase A using TC-A2317 is a promising target for anti-cancer therapeutics.


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