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Sphingosine kinase 1 promotes tumour cell migration and invasion via the S1P/EDG1 axis in hepatocellular carcinoma

Authors

  • Meiyan Bao,

    1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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    • These authors contributed equally to this work.
  • Zhiao Chen,

    1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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    • These authors contributed equally to this work.
  • Yongfen Xu,

    1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Yingjun Zhao,

    1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Ruopeng Zha,

    1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Shenglin Huang,

    1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Li Liu,

    1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Taoyang Chen,

    1. Qi Dong Liver Cancer Institute, Jiangsu, China
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  • Jinjun Li,

    1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Hong Tu,

    1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Xianghuo He

    Corresponding author
    • State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Correspondence

Xianghuo He PhD, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No.25/Ln.2200, Xie Tu Road, Shanghai 200032, China

Tel/Fax: +86 21 64436539

e-mail: xhhe@shsci.org

Abstract

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 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.

Discussion and conclusion

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.

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