A CERTain role for ceramide in taxane-induced cell death.
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.
Kolesnick
Richard
R
Program of Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. r-kolesnick@ski.mskcc.org
Altieri
Dario
D
Fuks
Zvi
Z
D001952:Bridged-Ring Compounds / Q000494:pharmacology; D016923:Cell Death; D002518:Ceramides / Q000378:metabolism*; D043171:Chromosomal Instability; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D008938:Mitosis; D017239:Paclitaxel / Q000494:pharmacology*; D011123:Polyploidy; D017510:Protein Folding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D034741:RNA, Small Interfering / Q000494:pharmacology; D008941:Spindle Apparatus / Q000502:physiology; D043823:Taxoids / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D001952:Bridged-Ring Compounds; D002518:Ceramides; D034741:RNA, Small Interfering; D043823:Taxoids; C080625:taxane; C119090:CERT1 protein, human; D017346:Protein Serine-Threonine Kinases; D017239:Paclitaxel