Abstract
G-protein-coupled receptor 120 (GPR120) is identified as a G-protein-coupled receptor for unsaturated long-chain free fatty acids that mediates insulin signaling and anti-inflammatory effects. Recently, it has been reported that GPR120 promotes the cell motile activity and angiogenesis in cancer cells. In this study, we assessed the role of GPR120 in the cell motile activity induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in rat liver epithelial WB-F344 cells. Cells were treated with TPA at a concentration of 5 nM for 72 h. The expression level of the Gpr120 gene was measured by quantitative real-time RT-PCR analysis. Cells treated with TPA showed the elevated Gpr120 expression, in comparison with untreated cells. In cell motility assays, the cell motile activity of cells treated with TPA was significantly higher than that of untreated cells. To confirm whether GPR120 is involved in the cell motile activity mediated by TPA, we generated GPR120 knockdown cells from WB-F344 cells. The cell motile activity induced by TPA was significantly suppressed by GPR120 knockdown. These results suggest that GPR120 plays an important role in the cell motile activity induced by TPA in WB-F344 cells.
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Venkatakrishnan AJ, Deupi X, Lebon G, Tate CG, Schertler GF, Babu MM (2013) Molecular signatures of G-protein-coupled receptors. Nature 494:185–194
Civelli O (2005) GPCR deorphanizations: the novel, the known and the unexpected transmitters. Trends Pharmacol Sci 26:15–19
Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE, Mortrud MT, Brown A, Rodriguez SS, Weller JR, Wright AC, Bergmann JE, Gaitanaris GA (2003) The G protein-coupled receptor repertoires of human and mouse. Proc Natl Acad Sci USA 100:4903–4908
Miyauchi S, Hirasawa A, Ichimura A, Hara T, Tsujimoto G (2010) New frontiers in gut nutrient sensor research: free fatty acid sensing in the gastrointestinal tract. J Pharmacol Sci 112:19–24
Hara T, Hirasawa A, Ichimura A, Kimura I, Tsujimoto G (2011) Free fatty acid receptors FFAR1 and GPR120 as novel therapeutic targets for metabolic disorders. J Pharm Sci 100:3594–3601
Talukdar S, Olefsky JM, Osborn O (2011) Targeting GPR120 and other fatty acid-sensing GPCRs ameliorates insulin resistance and inflammatory diseases. Trends Pharmacol Sci 32:543–550
Cornall LM, Mathai ML, Hryciw DH, McAinch AJ (2014) GPR120 agonism as a countermeasure against metabolic diseases. Drug Discov Today 19:670–679
Wu Q, Wang H, Zhao X, Shi Y, Jin M, Wan B, Xu H, Cheng Y, Ge H, Zhang Y (2013) Identification of G-protein-coupled receptor 120 as a tumor-promoting receptor that induces angiogenesis and migration in human colorectal carcinoma. Oncogene 32:5541–5550
Slaga TJ, Scribner JD, Viaje A (1976) Epidermal cell proliferation and promoting ability of phorbol esters. J Natl Cancer Inst 57:1145–1149
Yotti LP, Chang CC, Trosko JE (1979) Elimination of metabolic cooperation in Chinese hamster cells by a tumor promoter. Science 208:1089–1091
Murray AW, Fitzgerald DJ (1979) Tumor promoters inhibit metabolic cooperation in co-cultures of epidermal and 3T3 cells. Biochem Biophys Res Commun 91:395–401
Kavanagh TJ, Chang CC, Trosko JE (1986) Characterization of a human teratocarcinoma cell assay for inhibitors of metabolic cooperation. Cancer Res 46:1359–1366
Johnson MD, Torri JA, Lippman ME, Dickson RB (1999) Regulation of motility and protease expression in PKC-mediated induction of MCF-7 breast cancer cell invasiveness. Exp Cell Res 247:105–113
Lin CW, Hou WC, Shen SC, Juan SH, Ko CH, Wang LM, Chen YC (2008) Quercetin inhibition of tumor invasion via suppressing PKCδ/ERK/AP-1-dependent matrix metalloproteinase-9 activation in breast carcinoma cells. Carcinogenesis 29:1807–1815
Lin CW, Shen SC, Chien CC, Yang LY, Shia LT, Chen YC (2010) 12-O-tetradecanoylphorbol-13-acetate-induced invasion/migration of glioblastoma cells through activating PKCα/ERK/NF-κB-dependent MMP-9 expression. J Cell Physiol 225:472–481
Okabe K, Kato K, Teranishi M, Okumura M, Fukui R, Mori T, Fukushima N, Tsujiuchi T (2011) Induction of lysophosphatidic acid receptor-3 by 12-O-tetradecanoylphorbol-13-acetate stimulates cell migration of rat liver cells. Cancer Lett 309:236–242
Briscoe CP, Peat AJ, McKeown SC, Corbett DF, Goetz AS, Littleton TR, McCoy DC, Kenakin TP, Andrews JL, Ammala C, Fornwald JA, Ignar DM, Jenkinson S (2006) Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist small molecules. Br J Pharmacol 148:619–628
Tanabe E, Shibata A, Inoue S, Kitayoshi M, Fukushima N, Tsujiuchi T (2012) Regulation of cell motile activity through the different induction of LPA receptors by estrogens in liver epithelial WB-F344 cells. Biochem Biophys Res Commun 428:105–109
Hirasawa A, Tsumaya K, Awaji T, Katsuma S, Adachi T, Yamada M, Sugimoto Y, Miyazaki S, Tsujimoto G (2005) Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat Med 11:90–94
Oh SY, Madhukar BV, Trosko JE (1988) Inhibition of gap junctional blockage by palmitoyl carnitine and TMB-8 in a rat liver epithelial cell line. Carcinogenesis 9:135–139
Ren P, Mehta PP, Ruch RJ (1998) Inhibition of gap junctional intercellular communication by tumor promoters in connexin43 and connexin32-expressing liver cells: cell specificity and role of protein kinase C. Carcinogenesis 19:169–175
Tsujiuchi T, Araki M, Hirane M, Dong Y, Fukushima N (2014) Lysophosphatidic acid receptors in cancer pathobiology. Histol Histopathol 29:313–321
Hayashi M, Okabe K, Kato K, Okumura M, Fukui R, Fukushima N, Tsujiuchi T (2012) Differential function of lysophosphatidic acid receptors in cell proliferation and migration of neuroblastoma cells. Cancer Lett 316:91–96
Okabe K, Hayashi M, Kato K, Okumura M, Fukui R, Honoki K, Fukushima N, Tsujiuchi T (2013) Lysophosphatidic acid receptor-3 increases tumorigenicity and aggressiveness of rat hepatoma RH7777 cells. Mol Carcinog 52:247–254
Yu S, Murph MM, Lu Y, Liu S, Hall HS, Liu J, Stephens C, Fang X, Mills GB (2008) Lysophosphatidic acid receptors determine tumorigenicity and aggressiveness of ovarian cancer cells. J Natl Cancer Inst 100:1630–1642
Acknowledgments
This study was supported in part by a Grant-in-Aid (24590493) for Scientific Research (C) from Japan Society for the Promotion of Science, by Grants from the Ministry of Health, Labor and Welfare of Japan, and by Grants from the Faculty of Science and Engineering, Kinki University.
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Ishii, S., Hirane, M., Kitamura, Y. et al. Role of GPR120 in cell motile activity induced by 12-O-tetradecanoylphorbol-13-acetate in liver epithelial WB-F344 cells. Mol Cell Biochem 400, 145–151 (2015). https://doi.org/10.1007/s11010-014-2270-5
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DOI: https://doi.org/10.1007/s11010-014-2270-5