健康所研究人员发现脂肪酸受体调控肿瘤的新机制

 国际肿瘤研究权威杂志Oncogene近日在线发表了健康科学研究所张雁云研究组的最新研究成果：“Identification of G-Protein Coupled Receptor 120 as a Tumor-Promoting Receptor that Induces Angiogenesis ａnd Migration in Human Colorectal Carcinoma”。该研究首次揭示了脂肪酸受体G蛋白偶联受体120（G-protein coupled receptor 120, GPR120）在人结直肠癌进展中的作用及机制。

一系列GPR被认为是脂肪酸受体（free fatty acid receptor, FFAR），这些受体在生理性自稳中发挥着重要的作用。其中，GPR120是FFAR家族中最神秘的一个成员，其内源性配体为多不饱和长链脂肪酸。GPR120具有调节肠激素如缩胆囊素和胰高血糖素的分泌及炎症反应的作用。由于其在代谢性及炎症性疾病如肥胖，2型糖尿病中的潜在调节作用，GPR120的功能引起了广泛的关注。

张雁云研究员指导的博士后吴琼等发现GPR120在结直肠癌细胞株和人结直肠癌组织上高表达，且与肿瘤的进展密切相关；研究人员对GPR120在人结直肠癌进展中的作用及机制进行了深入研究，发现GPR120信号被活化后可促进肿瘤血管的生成及肿瘤的上皮间质化转化及迁移；同时，揭示了GPR120信号促进肿瘤血管生成的作用依赖于PI3K/Akt-NF-κB信号通路的活化。该研究首次揭示了GPR120是一种促进人类结直肠癌进展的FFAR，为脂质代谢组学与肿瘤发生发展的研究提供了新的理念，同时也提示GPR120是结直肠癌治疗的潜在重要靶点。

推荐英文摘要：

Oncogene doi: 10.1038/onc.2013.264

Identification of G-protein-coupled receptor 120 as a tumor-promoting receptor that induces angiogenesis ａnd migration in human colorectal carcinoma

Q Wu, H Wang, X Zhao, Y Shi, M Jin, B Wan, H Xu, Y Cheng, H Ge1 ａnd Y Zhang

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.