Stromal fibroblast activation protein alpha promotes gastric cancer progression via epithelial-mesenchymal transition through Wnt/ β-catenin pathway
Authors: Yan Li
Yonemura Yutaka
Fei Xu
Bin Xiong
Jiuyang Liu
Chaoqun Huang
Xiaojun Yang
Chunwei Peng
Journal: BMC Cancer (2018)
Discipline: CLINICAL MEDICINE
Keywords: Epithelial-mesenchymal transition; Fibroblast activation protein alpha; Gastric cancer; Peritoneal metastasis.
Affiliations: Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, China., Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, 430071, China., Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China., Department of General Surgery, Yingshan Renmin Hospital, Yingshan, 438700, China., Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China., Peritoneal Dissemination Center, Kishiwada Tokushukai Hospital, Kishiwada, 596-0032, Japan., Department of Surgery, Kusatsu General Hospital, Shiga, 600-8189, Japan., Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, China. ., Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, 430071, China. .

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. 

Retracted: No

PubPeer comments:
 Another hard-to-explain flow cytometry dot plot (Figure 3a; SGC FAP vs SGC NC). ![file] ,