GPR120 promotes metastasis but inhibits tumor growth in pancreatic ductal adenocarcinoma

Abstract

ObjectivesG-protein-coupled receptor 120 (GPR120) is a long-chain unsaturated fatty acid receptor, which regulates glucose metabolism and lipid. To date, there are disputes on the roles of GPR120 in the pathogenesis of cancer. Besides, little is known about its roles in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC). This study was designed to investigate the roles of GPR120 in the pathogenesis of PDAC. MethodsImmunohistochemical staining (IHC) was used for detecting the level of GPR120, epithelial-mesenchymal transformation (EMT) markers, Ki-67 and CD31 in ninety-one PDAC patients. Western blot, CCK8, flow cytometry and transwell assays were performed to determine proliferation, apoptosis, and motility in vitro. Subcutaneous tumor model was established to validate the roles of GPR120 in vivo. ResultsGPR120 was highly expressed in PDAC tissues, which was associated with free fatty acids (FFAs), lymph node metastasis (LNM), and poor prognosis. Moreover, GPR120 activation led to down-regulation of E-cadherin and up-regulation of Snail, Vimentin, N-cadherin, MMP2, MMP9, and CD31. Additionally, GPR120 decreased the expression of P-PI3K, P-AKT and CMYC and increased the level of P-JAK2, P-STAT3, Wnt5a, total β-catenin and β-catenin in nucleus. ConclusionsGPR120 promoted proliferation inhibition and apoptosis of PDAC, and contributed to PDAC metastasis via inducing EMT and angiogenesis. GPR120 served as a double-edged sword in the pathogenesis of PDAC.