title: Different effects of GPR120 and GPR40 on cellular functions stimulated by 12-O-tetradecanoylphorbol-13-acetate in melanoma cells.
abstract: G-protein-coupled receptor 120 (GPR120) and GPR40 exhibit a variety of biological responses by the binding of free fatty acids. 12-O-Tetradecanoylphorbol-13-acetate (TPA) is a tumor promoting agent of skin carcinogenesis. It is known that TPA treatment stimulates cell motile activity of cancer cells, including melanoma cells. In the present study, we investigated whether GRP120 and GPR40 are involved in regulation of cell motile activity induced by TPA in two melanoma cell lines. A375 and G361 cells were treated with TPA at a concentration of 10 nM for 24 h. The cell motile activity of A375 cells was significantly increased by TPA, correlating with GPR40 expression. In contrast, TPA suppressed the cell motile activity of G361 cells, while GPR120 and GPR40 expressions were increased. The cell motile activity of A375 cells treated with TPA was markedly increased by GPR120 knockdown. In addition, to assess roles of GPR120 and GPR40 in cellular functions of A375 cells by the long-term TPA treatment, cells were treated with TPA (1 nM) for at least 3 months. The long-term TPA treatment induced the high cell motile activity and elevated GPR120 and GPR40 expressions. The high cell motile activity of A375 cells stimulated by the long-term TPA treatment was enhanced by GPR120 knockdown. These results suggest that GPR120 negatively and GPR40 positively regulate cell motile activities induce by TPA in melanoma cells.
authors.affiliation: Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Fukushima
authors.affiliation: Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
authors.forename: Kaede
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Fukushima
authors.affiliation: Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Kanya
authors.initials: K
authors.lastname: Honoki
authors.affiliation: Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan. Electronic address: ttujiuch@life.kindai.ac.jp.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tsujiuchi
mesh_terms: D002273:Carcinogens / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism*
chemical_list: D002273:Carcinogens; C473034:FFAR1 protein, human; C519853:FFAR4 protein, human; D043562:Receptors, G-Protein-Coupled; D013755:Tetradecanoylphorbol Acetate
keywords: Cell motility; GPR120; GPR40; Melanoma cells; TPA