title: Netrin-1 promotes cell migration and invasion by down-regulation of BVES expression in human hepatocellular carcinoma.
abstract: 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, 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.
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Han
authors.affiliation: Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Jingmei
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Yunwu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Mengke
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Qinghai
authors.initials: Q
authors.lastname: Tan
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Dongxiao
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Yixing
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Jiqiao
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tu
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Dean
authors.initials: D
authors.lastname: Tian
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
keywords: AKT; BVES; Netrin-1; hepatocellular carcinoma; metastasis