Netrin-1 promotes cell migration and invasion by down-regulation of BVES expression in human hepatocellular carcinoma

American Journal of Cancer Research

Ping Han¹ 

关键词: Netrin-1;    hepatocellular carcinoma;    metastasis;    BVES;    AKT;   

DOI  :  

学科分类：肿瘤学

来源: e-Century Publishing Corporation

【 摘 要 】

The axon guidance cues netrin-1 has been reported to be associated with cancer progression in various types of human cancers. However, the underlying molecular mechanism of netrin-1-mediated metastasis remains obscure. In this study, we found that overexpression of netrin-1 promoted HCC cell migration and invasion as determined by transwell assay and 3D cell culture assay. However, netrin-1 knockdown inhibited these processes. Further investigation indicated that netrin-1 decreased the expression of Blood Vessel Epicardial Substance (BVES), which was down-regulated in HCC. Interestingly, {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002, a special inhibitor to PI3K/AKT signaling which was determined as a downstream pathway of netrin-1, restored the reduction in BVES caused by netrin-1. In addition, BVES exhibited an opposite effect on HCC cell metastasis to that of netrin-1. Importantly, up-regulating BVES expression significantly attenuated netrin-1-enhanced migration and invasion, whereas silencing BVES expression rescued the metastatic phenotype in netrin-1 knockdown cells. Moreover, netrin-1 expression was negatively correlated with BVES in HCC tissues and cell lines with different metastatic potential. Taken together, these results reveal that netrin-1 promotes HCC cell metastasis by regulating BVES expression via AKT activation.

【 授权许可】

CC BY-NC