The role of sphingosine kinase 1 in cancer: oncogene or non-oncogene addiction?
Sphingosine kinase 1 (SphK1) is a lipid kinase that catalyses the phosphorylation of sphingosine to sphingosine-1-phosphate. There is strong evidence from cellular or animal systems that SphK1 is involved in the major mechanisms underpinning oncogenesis, namely, the promotion of cellular survival, proliferation and transformation, the prevention of apoptosis and the stimulation of angiogenesis. Furthermore there is also good evidence from clinical samples that SphK1 is overexpressed in many, if not most tumor types examined and that many inhibitors of SphK1 render tumors sensitive to chemotherapeutic agents. A major question that remains concerns the exact mechanism of action of SphK1 in cancer. The tools available to probe SphK1 function perturb a set of cellular functions, and it is possible that several of these are involved in driving its oncogenic role. Furthermore, the importance of SphK1 functions in normal physiology and the lack of mutations of SphK1 in cancer, suggest that the mechanism in cancer might be an over reliance on this system of cellular signaling; an example of non-oncogene addiction.
Vadas
Mathew
M
Vascular Biology, Centenary Institute and Faculty of Medicine, University of Sydney, Australia. m.vadas@centenary.org.au
Xia
Pu
P
McCaughan
Geoff
G
Gamble
Jennifer
J
D000818:Animals; D017209:Apoptosis; D015972:Gene Expression Regulation, Neoplastic; D006262:Health; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D000099157:Sphingosine Kinase
D015513:Oncogene Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D000099157:Sphingosine Kinase