FPR2 promotes invasion and metastasis of gastric cancer cells and predicts the prognosis of patients.
FPR2 promotes invasion and metastasis of gastric cancer cells and predicts the prognosis of patients.
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FPR2促进胃癌细胞侵袭转移并预测患者预后
DOI：
10.1038/s41598-017-03368-7
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发表时间：
2017-06-09
影响因子：
4.6
通讯作者：
Liu W
中科院分区：
文献类型：
--
作者：
Hou XL;Ji CD;Tang J;Wang YX;Xiang DF;Li HQ;Liu WW;Wang JX;Yan HZ;Wang Y;Zhang P;Cui YH;Wang JM;Bian XW;Liu W
甲酰肽受体2(FPR2)是一种经典的G蛋白偶联受体趋化受体，已有报道参与某些肿瘤的侵袭和转移，但FPR2在胃癌中的作用尚未阐明。在本研究中，我们发现FPR2在胃癌中的表达水平与胃癌的侵袭深度、淋巴结转移呈正相关，与患者的总生存期呈负相关。多因素分析显示，FPR2表达是影响GC患者预后的独立指标。FPR2基因敲除显著抑制了Hp(2-20)和Ac(2-26)这两种FPR2配体在GC细胞中的迁移和侵袭。FPR2缺失也降低了体内GC细胞的致瘤和转移能力。在机制上，FPR2配体刺激导致E-钙粘蛋白表达下调，Vimentin表达上调，FPR2表达下调可逆转上述作用，提示参与了上皮-间充质转化(EMT)。此外，FPR2的激活伴随着ERK1/2的磷酸化，这种作用可被FPR2沉默或用MEK抑制剂PD98059处理而减弱。总之，我们的结果表明，FPR2在功能上参与了胃癌的侵袭和转移，并可能作为一种新的预后标志物和潜在的治疗靶点。
Formyl peptide receptor 2 (FPR2), a classical chemoattractant receptor of G-protein-coupled receptors, is reported to be involved in invasion and metastasis of some cancers, but the role of FPR2 in gastric cancer (GC) has not yet been elucidated. In this study, we found that the levels of FPR2 expression in GC were positively correlated with invasion depth, lymph node metastasis and negatively correlated with the patients’ overall survival. Multivariate analysis indicated that FPR2 expression was an independent prognostic marker for GC patients. FPR2-knockdown significantly abrogated the migration and invasion stimulated by Hp(2–20) and Ac(2–26), two well-characterized ligands for FPR2 in GC cells. FPR2 deletion also reduced the tumorigenic and metastatic capabilities of GC cells in vivo. Mechanistically, stimulation with FPR2 ligands resulted in down-regulation of E-cadherin and up-regulation of vimentin, which were reversed by FPR2 knock-down, implying the involvement of epithelial–mesenchymal transition (EMT). Moreover, the activation of FPR2 was accompanied with ERK1/2 phosphorylation, which could be attenuated by FPR2 silencing or treatment with MEK inhibitor, PD98059. Altogether, our results demonstrate that FPR2 is functionally involved in invasion and metastasis, and potentially acts as a novel prognostic marker as well as a potential therapeutic target in human GC.