These authors contributed equally to this work.
Sphingosine kinase 1 promotes tumour cell migration and invasion via the S1P/EDG1 axis in hepatocellular carcinoma
Article first published online: 30 OCT 2011
© 2011 John Wiley & Sons A/S
Volume 32, Issue 2, pages 331–338, February 2012
How to Cite
Bao, M., Chen, Z., Xu, Y., Zhao, Y., Zha, R., Huang, S., Liu, L., Chen, T., Li, J., Tu, H. and He, X. (2012), Sphingosine kinase 1 promotes tumour cell migration and invasion via the S1P/EDG1 axis in hepatocellular carcinoma. Liver International, 32: 331–338. doi: 10.1111/j.1478-3231.2011.02666.x
- Issue published online: 9 JAN 2012
- Article first published online: 30 OCT 2011
- Manuscript Accepted: 12 SEP 2011
- Manuscript Received: 4 APR 2011
- The Ministry of Health of China. Grant Number: 2008ZX10002-022
- Doctoral Program Foundation of Institutions of Higher Education of China. Grant Number: 20100073120108
- hepatocellular carcinoma;
- sphingosine kinase 1 (SphK1)
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.
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.