Ceramide kinase regulates growth and survival of A549 human lung adenocarcinoma cells.
Ceramide-1-phosphate (C1P) is emerging as a new addition to the family of bioactive sphingolipid metabolites. At low concentrations, C1P enhanced survival of NIH 3T3 fibroblasts and A549 lung cancer cells, while at high concentrations, it reduced survival and induced apoptosis. Apoptosis correlated with degradation of C1P to pro-apoptotic ceramide. To examine the role of endogenous C1P, expression of ceramide kinase, the enzyme that produces C1P, was downregulated, which reduced cellular proliferation, progression into S phase and enhanced apoptosis induced by serum starvation. Our results suggest that ceramide kinase determines the balance between pro-apoptotic ceramide and anti-apoptotic C1P to regulate cell fate, reminiscent of its function in plants.
Mitra
Poulami
P
Department of Biochemistry and Massey Cancer Center, Virginia Commonwealth University School of Medicine, 2-011 Sanger Hall, 1101 E. Marshall Street, Richmond, VA 23298-0614, USA.
Maceyka
Michael
M
Payne
Shawn G
SG
Lamour
Nadia
N
Milstien
Sheldon
S
Chalfant
Charles E
CE
Spiegel
Sarah
S
D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D051379:Mice; D041681:NIH 3T3 Cells; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism
D002518:Ceramides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C065576:ceramide 1-phosphate; D004815:Epidermal Growth Factor; D017853:Phosphotransferases (Alcohol Group Acceptor); C066324:ceramide kinase