Sprouty2 correlates with favorable prognosis of gastric adenocarcinoma via suppressing FGFR2-induced ERK phosphorylation and cancer progression
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Yunfei Xu1,*, Xiaoqing Yang2,*, Zhen Li3, Shuo Li5, Sen Guo1, Sayed Ismail1, Hongda Liu1, Zhihong Huang4, Zongli Zhang1, Yuxin Chen1, Qing Sun2
1Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong, China
2Department of Pathology, Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong, China
3Department of Neurology, Yidu Central Hospital of Weifang City, Weifang, Shandong, China
4Department of Neurosurgery, Yidu Central Hospital of Weifang City, Weifang, Shandong, China
5302 Hospital of People's Liberation Army, Beijing, China
*These authors contributed equally to this work
Zongli Zhang, email: email@example.com
Yuxin Chen, email: firstname.lastname@example.org
Keywords: gastric adenocarcinoma, FGFR2, SPRY2, proliferation, invasion
Received: December 26, 2015 Accepted: November 30, 2016 Published: December 16, 2016
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.
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