Identification Of G Protein-coupled Receptor 120 As A Tumor Promoting Receptor That Induces Angiogenesis And Migration In Human Colorectal Carcinoma

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 promotesangiogenesis 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-kB pathway is activated by GPR120 signaling and is required for GPR120signaling-induced angiogenic switching in CRC cells.And,GPR120 activationenhances 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 atumor-promoting receptor in CRC and,therefore,shows promise as a new potential target for cancer therapeutics.