title: Identification of G-protein-coupled receptor 120 as a tumor-promoting receptor that induces angiogenesis and migration in human colorectal carcinoma.
abstract: 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.
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institute of Immunology, Institutes of Medical Sciences, SJTUSM, Shanghai, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Wu
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
authors.forename: M
authors.initials: M
authors.lastname: Jin
authors.forename: B
authors.initials: B
authors.lastname: Wan
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.forename: Y
authors.initials: Y
authors.lastname: Cheng
authors.forename: H
authors.initials: H
authors.lastname: Ge
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis; D004789:Enzyme Activation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D015820:Cadherins; C519853:FFAR4 protein, human; D016209:Interleukin-8; D016328:NF-kappa B; D043562:Receptors, G-Protein-Coupled; D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D015232:Dinoprostone