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

Journal Article · Fri Oct 14 04:00:00 EDT 2016 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2016.09.060· OSTI ID:22696645

Huang, Miao ^[1]; Wu, Shengming ^[2]; Hu, Qiping ^[3]; Wu, Huayu; Wei, Shu; Xie, Huiqiong; Sun, Kejian; Li, Xiaolong; Fang, Ling ^[3]

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1. Radiology Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, 530021 (China)
2. Department of Pathology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, 530021 (China)
3. Department of Cell Biology and Genetics, School of Pre-clinical Medicine, Guangxi medical university, Nanning, 530021 (China)

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. - Highlights: • We found for the first time that SVAE may inhibit the migration and invasion of liver cancer cells. • The inhibition of migration and invasion was associated with the inversion of EMT. • The inversion of EMT was induced by Wnt/β-catenin signaling inhibition.

• OSTI ID: 22696645
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 479; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
INHIBITION
LIVER
MIGRATION
NEOPLASMS
SIGNALS
TRANSCRIPTION FACTORS