Identification of G-protein-coupled receptor 120 as a tumor-promoting receptor that induces angiogenesis and migration in human colorectal carcinoma
Identification of G-protein-coupled receptor 120 as a tumor-promoting receptor that induces angiogenesis and migration in human colorectal carcinoma
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鉴定 G 蛋白偶联受体 120 作为肿瘤促进受体，可诱导人结直肠癌中的血管生成和迁移
DOI：
10.1038/onc.2013.264
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发表时间：
2013-12-05
期刊：
影响因子：
8
通讯作者：
Zhang, Y.
中科院分区：
文献类型：
--
作者：
Wu, Q.;Wang, H.;Zhang, Y.
G蛋白偶联受体120(GPR120)是不饱和长链游离脂肪酸的受体，在调节糖脂代谢中起着重要作用。然而，GPR120在肿瘤发生发展中的作用尚未阐明。在这里，我们发现GPR120信号促进了人结直肠癌(CRC)细胞的血管生成转换和运动。我们发现，GPR120在结直肠癌组织和细胞系中的表达被显著诱导，这与肿瘤的进展有关。GPR12 0信号的激活在体外和体内均可促进血管生成，主要通过诱导血管生成介质如血管内皮生长因子、白介素8和环氧合酶2衍生的前列腺素E 2的表达和分泌来促进血管生成。PI3K/Akt-NF-κB通路由GPR12 0信号激活，在GPR12 0信号诱导的结直肠癌细胞血管生成转换中起重要作用。而且，GPR120的激活增强了结直肠癌细胞的运动能力，并诱导了上皮向间充质的转化。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，我们发现结直肠癌组织中GPR120的表达与血管内皮生长因子的表达呈正相关，与上皮标志物E-钙粘附素的表达呈负相关。总之，我们的结果表明GPR120在结直肠癌中作为肿瘤促进受体发挥作用，因此有望成为癌症治疗的新的潜在靶点。
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 E 2. 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.