title: Sphingosine kinase 1 promotes tumour cell migration and invasion via the S1P/EDG1 axis in hepatocellular carcinoma.
abstract: OBJECTIVE
  Sphingosine kinase 1 (SphK1), which phosphorylates sphingosine to sphingosine-1-phosphate (S1P), is overexpressed in various types of cancers, and may act as an oncogene in tumorigenesis. However, little is known about the precise role of the SphK1/S1P pathway in human liver cancer, especially regarding the metastasis of hepatocellular carcinoma (HCC).
  
  
  METHODS
  The expression of SphK1 was detected by quantitative reverse-transcription PCR. In addition, transwell cell migration and invasion assay were carried out for functional analysis. Furthermore, the level of S1P was quantified by ELISA and Rac1/Cdc42 GTPase activation was assessed by western blot analysis.
  
  
  RESULTS
  The levels of SphK1 mRNA are commonly up-regulated in HCC patients and human liver cancer cell migration and invasion can be promoted by the overexpression of SphK1. In addition, inhibition of SphK1 with either a SphK1 inhibitor or siRNA reduced human liver cancer cell migration and invasion. Furthermore, overexpression of SphK1 increased S1P levels, and the exogenous addition of S1P increased liver cell migration and invasion through the EDG1 receptor.
  
  
  CONCLUSIONS
  The results from this study provide strong evidence of a role for the SphK1/S1P/EDG1 pathway in liver metastasis, thus making it an attractive therapeutic target for the development of new anti-HCC drugs.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Meiyan
authors.initials: M
authors.lastname: Bao
authors.forename: Zhiao
authors.initials: Z
authors.lastname: Chen
authors.forename: Yongfen
authors.initials: Y
authors.lastname: Xu
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Ruopeng
authors.initials: R
authors.lastname: Zha
authors.forename: Shenglin
authors.initials: S
authors.lastname: Huang
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Taoyang
authors.initials: T
authors.lastname: Chen
authors.forename: Jinjun
authors.initials: J
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Tu
authors.forename: Xianghuo
authors.initials: X
authors.lastname: He
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000378:metabolism*; D000081025:Sphingosine-1-Phosphate Receptors; D014162:Transfection; D014407:Tumor Cells, Cultured; D000099157:Sphingosine Kinase
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); D034741:RNA, Small Interfering; D049349:Receptors, Lysosphingolipid; D000081025:Sphingosine-1-Phosphate Receptors; D000099157:Sphingosine Kinase; C477362:S1PR1 protein, human