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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Stromal fibroblast activation protein alpha promotes gastric cancer progression via epithelial-mesenchymal transition through Wnt/ β-catenin pathway

Authors: Jiuyang Liu, Chaoqun Huang, Chunwei Peng, Fei Xu, Yan Li, Yonemura Yutaka, Bin Xiong, Xiaojun Yang

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

To investigate the influence of fibroblast activation protein alpha (FAP) derived from cancer-associated fibroblasts (CAFs), as well as potential mechanism of epithelial mesenchymal transition (EMT), on gastric cancer (GC) progression.

Methods

Correlation between CAFs-derived FAP and clinical results has been studied by using 60 GC cases. To confirm this relationship, SGC7901 cells were co-cultured with pre-established FAP-overexpressed fibroblasts in vitro and the characteristics including proliferation, migration, invasion and apoptosis abilities were detected subsequently. Meanwhile, SGC and GES1 cells cocultured with FAP-overexpressed fibroblasts were treated with cis-platinum for apoptotic analysis. The underlying EMT was detected by analyzing expression level of E-cadherin, ZO-1, N-cadherin, Vimentin, α-SMA, DKK1 and LEF-1 through western blot and immunofluorescence staining assay. Finally, the tumor-promoting ability of FAP was investigated by utlizing a xenograft gastric cancer nude mouse model.

Results

It show that FAP has a high-risk correlation with the malignant level of clinical outcomes in GC patients. FAP promotes the ability of proliferation, migration, invasion, apoptosis-inhibition of SGC7901 cells and induces apoptosis of GES1 cells in vitro. The mechanism study shows that epithelial markers have been down-regulated and mesenchymal markers and Wnt/β-catenin signal pathway related proteins have been up-regulated. Animal assay suggests that tumor burden has been enhanced by FAP significantly in vivo.

Conclusions

Stromal FAP could be a potential prognostic biomarker in GC by promoting cancer progression via EMT through Wnt/ β-catenin signal pathway.
Appendix
Available only for authorised users
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Metadata
Title
Stromal fibroblast activation protein alpha promotes gastric cancer progression via epithelial-mesenchymal transition through Wnt/ β-catenin pathway
Authors
Jiuyang Liu
Chaoqun Huang
Chunwei Peng
Fei Xu
Yan Li
Yonemura Yutaka
Bin Xiong
Xiaojun Yang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-5035-9

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