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

• Main Authors: Jiuyang Liu, Chaoqun Huang, Chunwei Peng, Fei Xu, Yan Li, Yonemura Yutaka, Bin Xiong, Xiaojun Yang
• Format: Article
• Language: English
• Published: BMC 2018-11-01
• Series: BMC Cancer
• Subjects: Gastric cancer; Peritoneal metastasis; Fibroblast activation protein alpha; Epithelial-mesenchymal transition
• Online Access: http://link.springer.com/article/10.1186/s12885-018-5035-9

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.