Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institute of Immunology, Institutes of Medical Sciences, SJTUSM, Shanghai, China.
Oncogene. 2013 Dec 5;32(49):5541-50. doi: 10.1038/onc.2013.264. Epub 2013 Jul 15.
G-protein-coupled receptor 120 (GPR120) functions as a receptor for unsaturated long-chain free fatty acids and has an important role in regulating lipid and glucose metabolism. However, a role for GPR120 in the development of tumors has not yet been clarified. Here, we show that GPR120 signaling promotes angiogenic switching and motility of human colorectal carcinoma (CRC) cells. We show that the expression of GPR120 is significantly induced in CRC tissues and cell lines, which is associated with tumor progression. Activation of GPR120 signaling in human CRC promotes angiogenesis in vitro and in vivo, largely by inducing the expression and secretion of proangiogenic mediators such as vascular endothelial growth factor (VEGF), interleukin-8 and cyclooxygenase-2-derived prostaglandin E2. The PI3K/Akt-NF-κB pathway is activated by GPR120 signaling and is required for GPR120 signaling-induced angiogenic switching in CRC cells. And, GPR120 activation enhances the motility of CRC cells and induces epithelial-mesenchymal transition. Furthermore, in vivo study shows that activation of GPR120 promotes angiogenesis and tumor growth. Finally, we find that GPR120 expression is positively correlated with VEGF expression and inversely correlated with the epithelial marker E-cadherin in CRC tissues. Collectively, our results demonstrate that GPR120 functions as a tumor-promoting receptor in CRC and, therefore, shows promise as a new potential target for cancer therapeutics.
G 蛋白偶联受体 120（GPR120）作为不饱和长链游离脂肪酸的受体发挥作用，在调节脂质和葡萄糖代谢方面具有重要作用。然而，GPR120 在肿瘤发展中的作用尚未阐明。在这里，我们表明 GPR120 信号促进人结直肠癌（CRC）细胞的血管生成转换和运动。我们表明，GPR120 的表达在 CRC 组织和细胞系中显著诱导，这与肿瘤进展相关。GPR120 信号在人 CRC 中的激活在体外和体内均促进血管生成，主要通过诱导血管内皮生长因子（VEGF）、白细胞介素-8 和环氧化酶-2 衍生的前列腺素 E2 等促血管生成介质的表达和分泌。PI3K/Akt-NF-κB 途径被 GPR120 信号激活，并且是 GPR120 信号诱导 CRC 细胞血管生成转换所必需的。并且，GPR120 激活增强了 CRC 细胞的运动性并诱导上皮-间充质转化。此外，体内研究表明 GPR120 的激活促进了血管生成和肿瘤生长。最后，我们发现 GPR120 的表达与 CRC 组织中的 VEGF 表达呈正相关，与上皮标志物 E-钙黏蛋白呈负相关。总之，我们的结果表明 GPR120 在 CRC 中作为促肿瘤受体发挥作用，因此有望成为癌症治疗的新潜在靶点。
