FTY720 is an immunomo
dulator that is phosphorylate
d in vivo an
d inhibits lymphocyte mobilization by targeting sphingosine 1-phospate receptors. At
doses higher than require
d for immunomo
dulation, FTY720 inhibits tumor progression through an unknown mechanism. Here we show that FTY720-phosphate is a competitive inhibitor (
Ki ![](http://www.science<font color=)
direct.com/sci
dirimg/entities/223c.gif" alt="not, vert, similar" title="not, vert, similar" bor
der="0">0.2 μM) of autotaxin (ATX or NPP2), a nucleoti
de phospho
diesterase/pyrophosphatase (NPP) that enhances metastasis an
d angiogenesis an
d acts as a
lysophospholipase D to pro
duce the lipi
d me
diator lysophosphati
dic aci
d (LPA). FTY720-phosphate
di
d no affect the activity of NPP1, the closest relative of ATX. After oral a
dministration in mice, FTY720 (3 mg/kg) significantly re
duce
d plasma LPA levels. These results suggest that FTY720 may exert its anticancer effects, at least in part, by targeting the ATX-LPA axis.