BVES inhibition triggers epithelial-mesenchymal transition in human hepatocellular carcinoma

Ping Han, Yu Fu, Min Luo, Jiayi He, Jingmei Liu, Jiazhi Liao, Dean Tian, Wei Yan
Digestive Diseases and Sciences 2014, 59 (5): 992-1000

BACKGROUND/AIM: Metastasis contributes to the poor prognosis of hepatocellular carcinoma (HCC). However, the mechanism through which a primary HCC cell develops into a metastatic phenotype is not well understood. In this study, we set out to elucidate how blood vessel epicardial substance (BVES), a novel adhesion molecule regulating tight junction formation, mediates invasion and metastasis in human HCC cells.

METHODS: qRT-PCR, western blot and IHC were used to detect the expression of BVES in HCC samples and HCC cell lines. Small interfering RNAs (siRNAs) against human BVES were synthesized and used to transfect Huh7 cells. Then, the interference efficiency and the expression of mesenchymal marker vimentin and epithelial marker E-cadherin were measured by qRT-PCR and western blot. F-actin cytoskeleton was detected using TRITC-conjugated phalloidin. After inhibition of BVES, wound healing experiment and transwell assay were used to analyze the migratory and invasive ability of Huh7 cells.

RESULTS: BVES was down-regulated in human HCC tissues and HCC cell lines with high metastatic potential. After BVES inhibition, Huh7 cells exhibited some morphological changes including cytoskeleton rearrangement and junctional disruption. Cell migration and invasion were increased concomitant with increased expression of vimentin, IL-6, MMP2, MMP9 and decreased expression of E-cadherin. Finally, we found the expression of epithelial-mesenchymal transition (EMT) transcription factors Snail1 and Twist1 was significantly increased in BVES knockdown cells.

CONCLUSIONS: Our results suggest that down-regulation of BVES in HCC induces EMT, thus promoting invasion and metastasis in HCC cells.

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