S1P/S1P1 signaling stimulates cell migration and invasion in Wilms tumor

Sphingosine-1-phosphate (S1P) is an important regulator of cellular functions via interaction with its receptors S1P1–5. To date, nothing is known about the S1P receptor expression and the effects of S1P signaling in Wilms tumor. In this study, we found ubiquitous expression of S1P receptors in Wilms tumor specimens and cell lines. We demonstrated that S1P1 acted as a promigratory modulator by employing S1P1 antagonist VPC44116, S1P1 siRNA and adenoviral transduction in Wilms tumor cells. Further, we clarified that S1P1-mediated migration occurred via Gi coupling and activation of PI3K and Rac1. In addition, S1P stimulated WiT49 cell invasion through S1P1/Gi signaling pathway. We consider that targeting S1P1 may be a point of therapeutic intervention in Wilms tumor.