GPR120 promotes metastasis but inhibits tumor growth in pancreatic ductal adenocarcinoma

被引:5
作者
Sun, Xiaoyuan [1 ]
Chu, Huijun [2 ]
Lei, Ke [3 ]
Ci, Yandong [4 ]
Lu, Haijun [5 ]
Wang, Jia [3 ]
Zhou, Meng [1 ]
Ren, He [3 ]
Zheng, Tongsen [1 ]
机构
[1] Harbin Med Univ, Canc Hosp, Dept Gastrointestinal Med Oncol, Harbin 150081, Peoples R China
[2] Qingdao Univ, Affiliated Hosp, Dept Gynecol, Qingdao 266003, Peoples R China
[3] Qingdao Univ, Affiliated Hosp, Ctr Tumor Immunol & Cytotherapy, Dept Gastroenterol,Med Res Ctr, Qingdao 266003, Peoples R China
[4] Qingdao Eighth Peoples Hosp, Dept Orthoped, Qingdao 266003, Peoples R China
[5] Qingdao Univ, Affiliated Hosp, Dept Radiat Oncol, Qingdao 266003, Peoples R China
基金
中国国家自然科学基金;
关键词
G -protein -coupled receptor 120; Pancreatic ductal adenocarcinoma; Epithelial-mesenchymal transformation; Metastasis; Proliferation; CANCER; RECEPTOR; CHEMORESISTANCE; EPIDEMIOLOGY; MIGRATION; POTENT; FFA4;
D O I
10.1016/j.pan.2022.06.006
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Objectives: G-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.Methods: Immunohistochemical staining (IHC) was used for detecting the level of GPR120, epithelialmesenchymal 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.Results: GPR120 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 f3-catenin and f3-catenin in nucleus. Conclusions: GPR120 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.(c) 2022 IAP and EPC. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:749 / 759
页数:11
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