Roles of sphingosine 1-phosphate on tumorigenesis

Figure 3 Sphingosine 1-phosphate receptor subtype-specific signaling. Sphingosine 1-phosphate (S1P)₁, S1P₂, S1P₃, and S1P₅ activate partially overlapping downstream signaling via coupling different G proteins and then regulate several biological functions, such as cell proliferation, migration, angiogenesis, and autophagy. Through coupling to G_i protein, S1P₁ activates extracellular signal-regulated kinase (ERK)1/2, Rac, and phosphoinositide 3-kinase (PI3K) signaling to regulate cell proliferation, migration, and angiogenesis, respectively. S1P₂ mediates inhibition of cell migration via G_12/13-Rho signaling, whereas S1P₃ enhances cell migration and angiogenesis through G_i-Rac and G_q-phospholipase C (PLC) signaling, respectively. Our unpublished results have revealed that G_i coupled-S1P₅ induces autophagy which is mediated through PI3K and PLC signaling.