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Sphingosine kinase 1 promotes tumour cell migration and invasion via the S1P / EDG 1 axis in hepatocellular carcinoma
Author(s) -
Bao Meiyan,
Chen Zhiao,
Xu Yongfen,
Zhao Yingjun,
Zha Ruopeng,
Huang Shenglin,
Liu Li,
Chen Taoyang,
Li Jinjun,
Tu Hong,
He Xianghuo
Publication year - 2012
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2011.02666.x
Subject(s) - sphingosine kinase 1 , sphingosine , cancer research , sphingosine kinase , metastasis , oncogene , sphingosine 1 phosphate , cell migration , rac1 , biology , carcinogenesis , cell , kinase , cancer , cell growth , signal transduction , microbiology and biotechnology , cell cycle , receptor , biochemistry , genetics
Background/Aims 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 ).Materials and 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 GTP ase 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 si RNA 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 EDG 1 receptor.Discussion and conclusion The results from this study provide strong evidence of a role for the SphK1/S1P/ EDG 1 pathway in liver metastasis, thus making it an attractive therapeutic target for the development of new anti‐ HCC drugs.