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 S1P(1-5). 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 S1P(1) acted as a promigratory modulator by employing S1P(1) antagonist VPC44116, S1P(1) siRNA and adenoviral transduction in Wilms tumor cells. Further, we clarified that S1P(1)-mediated migration occurred via Gi coupling and activation of PI3K and Rac1. In addition, S1P stimulated WiT49 cell invasion through S1P(1)/Gi signaling pathway. We consider that targeting S1P(1) may be a point of therapeutic intervention in Wilms tumor.
Li
Mei-Hong
MH
Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
Sanchez
Teresa
T
Yamase
Harold
H
Hla
Timothy
T
Oo
Myat Lin
ML
Pappalardo
Anna
A
Lynch
Kevin R
KR
Lin
Chen-Yong
CY
Ferrer
Fernando
F
D045744:Cell Line, Tumor; D002465:Cell Movement; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology*; D008246:Lysophospholipids / Q000502:physiology*; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D049349:Receptors, Lysosphingolipid / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology; D009396:Wilms Tumor / Q000473:pathology*; D020830:rac1 GTP-Binding Protein / Q000502:physiology
D008246:Lysophospholipids; D034741:RNA, Small Interfering; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D019869:Phosphatidylinositol 3-Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020830:rac1 GTP-Binding Protein; D013110:Sphingosine