Li Mei-Hong, Sanchez Teresa, Yamase Harold, Hla Timothy, Oo Myat Lin, Pappalardo Anna, Lynch Kevin R, Lin Chen-Yong, Ferrer Fernando
Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
Cancer Lett. 2009 Apr 18;276(2):171-9. doi: 10.1016/j.canlet.2008.11.025. Epub 2009 Jan 7.
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.
鞘氨醇-1-磷酸(S1P)通过与其受体S1P(1-5)相互作用,是细胞功能的重要调节因子。迄今为止,关于S1P受体在肾母细胞瘤中的表达以及S1P信号传导的影响尚无定论。在本研究中,我们发现S1P受体在肾母细胞瘤标本和细胞系中普遍表达。我们通过在肾母细胞瘤细胞中使用S1P(1)拮抗剂VPC44116、S1P(1)小干扰RNA(siRNA)和腺病毒转导,证明S1P(1)作为一种促迁移调节因子发挥作用。此外,我们阐明S1P(1)介导的迁移是通过Gi偶联以及PI3K和Rac1的激活而发生的。另外,S1P通过S1P(1)/Gi信号通路刺激WiT49细胞侵袭。我们认为靶向S1P(1)可能是肾母细胞瘤治疗干预的一个靶点。