國際腫瘤研究權(quán)威雜志Oncogene近日在線發(fā)表了健康科學(xué)研究所張雁云研究組的最新研究成果：“Identification of G-Protein Coupled Receptor 120 as a Tumor-Promoting Receptor that Induces Angiogenesis and Migration in Human Colorectal Carcinoma”,。該研究首次揭示了脂肪酸受體G蛋白偶聯(lián)受體120（G-protein coupled receptor 120, GPR120）在人結(jié)直腸癌進(jìn)展中的作用及機(jī)制,。
一系列GPR被認(rèn)為是脂肪酸受體（free fatty acid receptor, FFAR），這些受體在生理性自穩(wěn)中發(fā)揮著重要的作用,。其中,，GPR120是FFAR家族中最神秘的一個成員，其內(nèi)源性配體為多不飽和長鏈脂肪酸,。GPR120具有調(diào)節(jié)腸激素如縮膽囊素和胰高血糖素的分泌及炎癥反應(yīng)的作用,。由于其在代謝性及炎癥性疾病如肥胖，2型糖尿病中的潛在調(diào)節(jié)作用,，GPR120的功能引起了廣泛的關(guān)注,。
張雁云研究員指導(dǎo)的博士后吳瓊等發(fā)現(xiàn)GPR120在結(jié)直腸癌細(xì)胞株和人結(jié)直腸癌組織上高表達(dá)，且與腫瘤的進(jìn)展密切相關(guān),；研究人員對GPR120在人結(jié)直腸癌進(jìn)展中的作用及機(jī)制進(jìn)行了深入研究,，發(fā)現(xiàn)GPR120信號被活化后可促進(jìn)腫瘤血管的生成及腫瘤的上皮間質(zhì)化轉(zhuǎn)化及遷移；同時,，揭示了GPR120信號促進(jìn)腫瘤血管生成的作用依賴于PI3K/Akt-NF-κB信號通路的活化,。該研究首次揭示了GPR120是一種促進(jìn)人類結(jié)直腸癌進(jìn)展的FFAR，為脂質(zhì)代謝組學(xué)與腫瘤發(fā)生發(fā)展的研究提供了新的理念,，同時也提示GPR120是結(jié)直腸癌治療的潛在重要靶點(diǎn),。（生物谷Bioon.com）
生物谷推薦英文摘要：
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.
