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Sprouty2 correlates with favorable prognosis of gastric adenocarcinoma via suppressing FGFR2-induced ERK phosphorylation and cancer progression

2016; Impact Journals LLC; Volume: 8; Issue: 3 Linguagem: Inglês

10.18632/oncotarget.13982

1949-2553

Yunfei Xu, Xiaoqing Yang, Zhen Li, Shuo Li, Sen Guo, Sayed Ismail, Hongda Liu, Zhihong Huang, Zongli Zhang, Yuxin Chen, Qing Sun,

Cancer, Hypoxia, and Metabolism

// Yunfei Xu 1, * , Xiaoqing Yang 2, * , Zhen Li 3 , Shuo Li 5 , Sen Guo 1 , Sayed Ismail 1 , Hongda Liu 1 , Zhihong Huang 4 , Zongli Zhang 1 , Yuxin Chen 1 , Qing Sun 2 1 Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong, China 2 Department of Pathology, Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong, China 3 Department of Neurology, Yidu Central Hospital of Weifang City, Weifang, Shandong, China 4 Department of Neurosurgery, Yidu Central Hospital of Weifang City, Weifang, Shandong, China 5 302 Hospital of People's Liberation Army, Beijing, China * These authors contributed equally to this work Correspondence to: Zongli Zhang, email: zzlzzl1900@163.com Yuxin Chen, email: cyxsdu2012@163.com Qing Sun, email: sunqqq2016@163.com , qingsw99@163.com Keywords: gastric adenocarcinoma, FGFR2, SPRY2, proliferation, invasion Received: December 26, 2015 Accepted: November 30, 2016 Published: December 16, 2016 ABSTRACT Fibroblast growth factor receptor 2 (FGFR2) has been identified as a predictive biomarker for unfavorable prognosis of gastric adenocarcinoma. As a well-defined antagonist in FGFR2-induced RAS/ERK activation, ectopic expression of sprouty (SPRY) family was reported in several kinds of cancers except gastric cancer. To explore the clinical significance of SPRY family and its correlation with FGFR2, we detected the expression of FGFR2 and SPRY family in 104 cases of gastric adenocarcinoma and subsequently analyzed their correlations with clinicopathological factors and overall survival rates by univariate and multivariate analysis. As the result, we demonstrated that both FGFR2 high-expression and SPRY2 low-expression indicated poorer prognosis of gastric adenocarcinoma. SPRY2 low-expression was significantly associated with FGFR2 high-expression, positive lymphatic invasion and metastasis. We further proved that SPRY2 could suppress FGFR2-induced ERK phosphorylation, cell proliferation and invasion with experiments in vitro and in vivo . In conclusion, we demonstrated that SPRY2 low-expression is a biomarker for unfavorable prognosis in gastric adenocarcinoma. SPRY2 can antagonize FGFR2-induced proliferation and invasion via suppressing ERK phosphorylation in gastric cancer cells, indicating SPRY2 as a potential therapeutic target for gastric adenocarcinoma treatment.