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  NEK9 depletion induces catastrophic mitosis by impairment of mitotic checkpoint control and spindle dynamics

Kaneta, Y., & Ullrich, A. (2013). NEK9 depletion induces catastrophic mitosis by impairment of mitotic checkpoint control and spindle dynamics. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 442(3-4), 139-146. doi:10.1016/j.bbrc.2013.04.105.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0015-1979-5 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0015-197A-3
Genre: Journal Article

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 Creators:
Kaneta, Yasuyuki1, Author              
Ullrich, Axel1, Author              
Affiliations:
1Ullrich, Axel / Molecular Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565172              

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Free keywords: CELL-CYCLE REGULATION; PROTEIN-KINASES; CANCER-CELLS; PROGRESSION; FAMILY; CYTOKINESIS; INSTABILITY; CENTROSOME; BINDING; NERCC1NEK9; Cytokinesis; Checkpoint system; Mitotic arrest; Therapeutic target;
 Abstract: NEK9 is known to play a role in spindle assembly and in the control of centrosome separation, but the consequences of NEK9 targeting in cancer cells remain to be elucidated. In this study, we used siRNA to investigate the consequences of targeting NEK9 in glioblastoma and kidney cancer cells as a first step in assessing its potential as an anti-cancer therapeutic target. Live cell imaging revealed that NEK9 depletion of U1242 glioblastoma and Caki2 kidney carcinoma cells resulted in failure of cytokinesis. Interestingly, NEK9-depleted Caki2 cells overrode mitosis under incorrect chromosome alignment and were converted to a micronucleated phenotype, leading to cell death. Whereas, the RPE1 normal epithelium cell line was refractory to abnormal mitosis upon NEK9 knockdown. Nocodazole-induced mitotic arrest was compromised after NEK9 depletion, indicating that NEK9 has an important role in mitotic checkpoint system. Taken together, we propose that NEK9 inhibition represents a novel anti-cancer strategy by induction of mitotic catastrophe via impairment of spindle dynamics, cytokinesis and mitotic checkpoint control. (C) 2013 Published by Elsevier Inc.

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Language(s): eng - English
 Dates: 2013
 Publication Status: Published in print
 Pages: 8
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Degree: -

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Title: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Source Genre: Journal
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Publ. Info: 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA : ACADEMIC PRESS INC ELSEVIER SCIENCE
Pages: - Volume / Issue: 442 (3-4) Sequence Number: - Start / End Page: 139 - 146 Identifier: ISSN: 0006-291X