期刊
ONCOGENE
卷 32, 期 49, 页码 5541-5550出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2013.264
关键词
GPR120; colorectal carcinoma; angiogenesis; migration
资金
- Ministry of Science and Technology of China [2011CB966200, 2010CB945600]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA01040000]
- Program of Chinese Academy of Sciences [KSCX1-YW-22]
- National Natural Science Foundation of China [81071748, 30873045, 81130057]
- China Postdoctoral Science Foundation [2012M510906]
- Leading Academic Discipline Project of Shanghai Municipal Education Commission [J50207]
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-kappa B 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.
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