title: Agkihpin, a novel SVAE may inhibit the migration and invasion of liver cancer cells associated with the inversion of EMT induced by Wnt/β-catenin signaling inhibition.
abstract: In our previous work, agkihpin, a snake venom arginine esterase (SVAE), was isolated from the Gloydius halys Pallas, which could attenuate the migration of liver cancer cells. However, the mechanism of the effect of agkihpin on attenuating migration of liver cancer cell is unknown yet. Here, to learn more about agkihpin and explore the possibility of agkihpin as an anti-metastatic drug in the future, a series of experiments about the migration and invasion of liver cancer cells with agkihpin, HepG 2 and SMMC-7721, was conducted. Epithelial-mesenchymal transition (EMT) is an initial step and a major phenotype of cancer metastasis and invasion, while a number of EMT opposite phenomenons were observed, for example, epithelial marker E-cadherin was up-regulated, mesenchymal markers N-cadherin and Vimentin, and transcription regulators Snail and twist were down-regulated after treating with agkihpin in liver cancer cells; canonical Wnt/β-catenin pathway, one of the signals initiated EMT, was inhibited by decreased expressions of FZD7 and β-catenin, phosphorylation of GSK3β (Ser9), and nuclear β-catenin accumulation in agkihpin treated cancer cells. By using bioinformatics analysis and protease activity analysis in vitro we also found that agkihpin might bind and degrade FZD7. As a result, we hypothesized that agkihpin could inhibit the Wnt/β-catenin signaling pathway by cleaving FZD7, leading to the inactivation of the TCF/LEF transcription factor, which contributed to the inversion of EMT, and finally attenuated the migration and invasion of liver cancer cells. Therefore, our findings provided novel mechanistic insights into the role of SVAEs in liver cancer controlling, and raised the possibility that agkihpin may be used therapeutically in liver cancer.
authors.affiliation: Radiology Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, PR China.
authors.forename: Miao
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Pathology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, PR China.
authors.forename: Shengming
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Cell Biology and Genetics, School of Pre-clinical Medicine, Guangxi medical university, Nanning, 530021, PR China. Electronic address: huqiping@gxmu.edu.cn.
authors.forename: Qiping
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Cell Biology and Genetics, School of Pre-clinical Medicine, Guangxi medical university, Nanning, 530021, PR China.
authors.forename: Huayu
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Cell Biology and Genetics, School of Pre-clinical Medicine, Guangxi medical university, Nanning, 530021, PR China.
authors.forename: Shu
authors.initials: S
authors.lastname: Wei
authors.affiliation: Department of Cell Biology and Genetics, School of Pre-clinical Medicine, Guangxi medical university, Nanning, 530021, PR China.
authors.forename: Huiqiong
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Cell Biology and Genetics, School of Pre-clinical Medicine, Guangxi medical university, Nanning, 530021, PR China.
authors.forename: Kejian
authors.initials: K
authors.lastname: Sun
authors.affiliation: Department of Cell Biology and Genetics, School of Pre-clinical Medicine, Guangxi medical university, Nanning, 530021, PR China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cell Biology and Genetics, School of Pre-clinical Medicine, Guangxi medical university, Nanning, 530021, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Fang
mesh_terms: D002265:Carboxylic Ester Hydrolases / Q000737:chemistry*; D002465:Cell Movement; D019295:Computational Biology; D004305:Dose-Response Relationship, Drug; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D011485:Protein Binding; D060888:Real-Time Polymerase Chain Reaction; D012910:Snake Venoms / Q000737:chemistry*; D060449:Wnt Signaling Pathway
chemical_list: D012910:Snake Venoms; C000619953:agkihpin protein, Gloydius halys; D002265:Carboxylic Ester Hydrolases
keywords: Agkihpin; Canonical Wnt/β-catenin pathway; Epithelial-mesenchymal transition (EMT); Liver cancer; Metastasis; Migration and invasion; Snake venom arginine esterase (SVAE)