Sphingosine-1-phosphate receptor 1 (S1PR1) expressed on EC-surface, like VEGFR2, is shown to mediate tumor angiogenesis.4 Upon ligating sphingosine 1 Phosphate (S1P), S1PR1 stimulates heterotrimeric protein, Gi which in turn activates PI3-kinase/Akt/ERK signaling leading to EC survival.5 S1PR1-Gi cascade also activates the small GTPase Rac1, which is essential for EC migration.6,7 While a few studies showed that impairment of S1PR1 function reduced VEGF-induced angiogenesis8 others showed that loss of S1PR1 in ECs induced hyper-sprouting due to increased VEGFR2 activity.9 This evidence concerns the gene KDR and neoplasm.