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

被引：114

作者：

Bao, Meiyan ^{[1
]}

Chen, Zhiao ^{[1
]}

Xu, Yongfen ^{[1
]}

Zhao, Yingjun ^{[1
]}

Zha, Ruopeng ^{[1
]}

Huang, Shenglin ^{[1
]}

Liu, Li ^{[1
]}

Chen, Taoyang ^{[2
]}

Li, Jinjun ^{[1
]}

Tu, Hong ^{[1
]}

He, Xianghuo ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, State Key Lab Oncogenes & Related Genes, Shanghai Canc Inst, Renji Hosp,Sch Med, Shanghai 200032, Peoples R China

[2] Qi Dong Liver Canc Inst, Qidong, Jiangsu, Peoples R China

来源：

LIVER INTERNATIONAL | 2012年 / 32卷 / 02期

关键词：

EDG1; hepatocellular carcinoma; invasion; migration; S1P; sphingosine kinase 1 (SphK1); PROTEIN-COUPLED RECEPTOR; CANCER CELLS; SPHINGOSINE-1-PHOSPHATE; 1-PHOSPHATE; PROLIFERATION; INHIBITION; EXPRESSION; ANGIOGENESIS; PROGRESSION; METASTASIS;

D O I：

10.1111/j.1478-3231.2011.02666.x

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

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. © 2011 John Wiley & Sons A/S.

引用

页码：331 / 338

页数：8

共 33 条

[1]

High expression of sphingosine kinase 1 and S1P receptors in chemotherapy-resistant prostate cancer PC3 cells and their camptothecin-induced up-regulation [J].