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Netrin-1 promotes cell migration and invasion by down-regulation of BVES
expression in human hepatocellular carcinoma
#MMPMID26101705
Han P
; Fu Y
; Liu J
; Wang Y
; He J
; Gong J
; Li M
; Tan Q
; Li D
; Luo Y
; Han J
; Liu J
; Tu W
; Wang Y
; Tian D
; Yan W
Am J Cancer Res
2015[]; 5
(4
): 1396-409
PMID26101705
show ga
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.
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