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Cancer Lett. 2014 Feb 28;343(2):232-8. doi: 10.1016/j.canlet.2013.09.036. Epub 2013 Oct 4.

Identification of a mitotic death signature in cancer cell lines.

Author information

1
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
2
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Electronic address: chamberstimothyc@uams.edu.

Abstract

This study examined the molecular mechanism of action of anti-mitotic drugs. The hypothesis was tested that death in mitosis occurs through sustained mitotic arrest with robust Cdk1 signaling causing complete phosphorylation of Mcl-1 and Bcl-xL, and conversely, that mitotic slippage is associated with incomplete phosphorylation of Mcl-1/Bcl-xL. The results, obtained from studying six different cancer cell lines, strongly support the hypothesis and identify for the first time a unique molecular signature for mitotic death. The findings represent an important advance in understanding anti-mitotic drug action and provide insight into cancer cell susceptibility to such drugs which has important clinical implications.

KEYWORDS:

Apoptosis; Bcl-2 proteins; Cancer cell lines; Mitotic arrest; Mitotic death; Phosphorylation

PMID:
24099917
PMCID:
PMC3947203
DOI:
10.1016/j.canlet.2013.09.036
[Indexed for MEDLINE]
Free PMC Article

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