Identification of a mitotic death signature in cancer cell lines

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • CDC2 Protein Kinase / antagonists & inhibitors
  • Cell Cycle / drug effects
  • Cell Cycle / physiology*
  • Cell Death / genetics
  • Cell Death / physiology*
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Flow Cytometry
  • Humans
  • Immunoblotting
  • Mitosis / drug effects
  • Myeloid Cell Leukemia Sequence 1 Protein / genetics
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism
  • Phosphorylation
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • bcl-X Protein / genetics
  • bcl-X Protein / metabolism

Substances

  • BCL2L1 protein, human
  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • bcl-X Protein
  • CDC2 Protein Kinase
  • Cisplatin