Journal
CURRENT MOLECULAR MEDICINE
Volume 12, Issue 10, Pages 1207-1219Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/156652412803833599
Keywords
Apoptosis; cancer; FTY720; fingolimod; lymphopenia; lysophospholipid; sphingosine; sphingosine 1-phosphate
Categories
Funding
- Fay Fuller Foundation [626936, 626937, 1004695]
- National Health and Medical Research Council of Australia [565217]
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FTY720 is a recently approved first line therapy for relapsing forms of multiple sclerosis. In this context, FTY720 is a pro-drug, with its anti-multiple sclerosis, immunosuppressive effects largely elicited following its phosphorylation by sphingosine kinase 2 and subsequent modulation of G protein-coupled sphingosine 1-phosphate (S1P) receptor 1 that induces lymphopenia by altering lymphocyte trafficking. A number of other biological effects of FTY720 have, however, been described, including considerable evidence that this drug also has anti-cancer properties. These other effects of FTY720 are independent of S1P receptors, and appear facilitated by modulation of a range of other recently described protein targets by non-phosphorylated FTY720. Here, we review the direct targets of FTY720 that contribute to its anti-cancer properties. We also discuss other recently described protein effectors that, in combination with S1P receptors, appear to contribute to its immunosuppressive effects.
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