A CERTain role for ceramide in taxane-induced cell death

Cancer Cell. 2007 Jun;11(6):473-5. doi: 10.1016/j.ccr.2007.05.003.

Abstract

An unexpected benefit of functional genomic screens is that at times they answer questions that they were not designed to ask. A siRNA screen reported by Swanton et al. in this issue of Cancer Cell reveals that silencing of spindle assembly checkpoint genes facilitates mitotic slippage, resulting in escape from taxane-induced cell death, aneuploidy, and chromosomal instability, hallmarks of taxane resistance. Unexpectedly, the screen disclosed that the sphingolipid ceramide is a key regulator of the taxane-mediated spindle assembly checkpoint and taxane-induced cell death. Ceramide metabolism thus serves as a legitimate target for modulation of taxane effect on tumors.

Publication types

  • Comment

MeSH terms

  • Bridged-Ring Compounds / pharmacology
  • Cell Death*
  • Ceramides / metabolism*
  • Chromosomal Instability
  • Drug Resistance, Neoplasm / genetics*
  • Humans
  • Mitosis
  • Paclitaxel / pharmacology*
  • Polyploidy
  • Protein Folding
  • Protein Serine-Threonine Kinases / genetics*
  • RNA, Small Interfering / pharmacology
  • Spindle Apparatus / physiology
  • Taxoids / pharmacology
  • Tumor Cells, Cultured

Substances

  • Bridged-Ring Compounds
  • Ceramides
  • RNA, Small Interfering
  • Taxoids
  • taxane
  • CERT1 protein, human
  • Protein Serine-Threonine Kinases
  • Paclitaxel