FPR2 promotes invasion and metastasis of gastric cancer cells and predicts the prognosis of patients

• Published in: Scientific reports 2017-06, Vol.7 (1), p.3153-11, Article 3153
• Main Authors: Hou, Xi-Lu, Ji, Cheng-Dong, Tang, Jun, Wang, Yan-Xia, Xiang, Dong-Fang, Li, Hai-Qing, Liu, Wei-Wei, Wang, Jiao-Xue, Yan, He-Zhong, Wang, Yan, Zhang, Peng, Cui, You-Hong, Wang, Ji-Ming, Bian, Xiu-Wu, Liu, Wei
• Format: Article
• Language: English
• Subjects: 13/1; 13/51; 38/77; 38/79; 38/89; 631/67/1504/1829; 631/67/1857; Aged; Animals; Antigens, CD - genetics; Antigens, CD - metabolism; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cadherins - genetics; Cadherins - metabolism; Cell Line, Tumor; Clonal deletion; Down-regulation; E-cadherin; Epithelial-Mesenchymal Transition; Female; G protein-coupled receptors; Gastric cancer; Gene Expression Regulation, Neoplastic; Humanities and Social Sciences; Humans; Ligands; Lymph nodes; Lymphatic Metastasis; Male; Medical prognosis; Mesenchyme; Metastases; Metastasis; Mice; Mice, Nude; Middle Aged; Mitogen-Activated Protein Kinase 1 - genetics; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - genetics; Mitogen-Activated Protein Kinase 3 - metabolism; multidisciplinary; Multivariate analysis; Neoplasm Grading; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Phosphorylation; Prognosis; Receptors, Formyl Peptide - antagonists & inhibitors; Receptors, Formyl Peptide - genetics; Receptors, Formyl Peptide - metabolism; Receptors, Lipoxin - antagonists & inhibitors; Receptors, Lipoxin - genetics; Receptors, Lipoxin - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Science; Science (multidisciplinary); Signal Transduction; Stomach Neoplasms - diagnosis; Stomach Neoplasms - genetics; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Survival Analysis; Vimentin; Vimentin - genetics; Vimentin - metabolism; Xenograft Model Antitumor Assays
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-03368-7

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.