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Negative effects of G‐protein‐coupled free fatty acid receptor GPR40 on cell migration and invasion in fibrosarcoma HT1080 cells
Author(s) -
Ishii Shuhei,
Kitamura Yuka,
Hirane Miku,
Tomimatsu Ayaka,
Fukushima Kaori,
Takahashi Kaede,
Fukushima Nobuyuki,
Honoki Kanya,
Tsujiuchi Toshifumi
Publication year - 2016
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22408
Subject(s) - ht1080 , free fatty acid receptor 1 , fibrosarcoma , biology , gpr120 , gene knockdown , cancer research , cell , biochemistry , cancer cell , cell migration , receptor , microbiology and biotechnology , cancer , agonist , g protein coupled receptor , gene , genetics
G‐protein‐coupled receptor 40 (GPR40) and GPR120 mediate a variety of biological functions by the binding of long and medium chain free fatty acids. In the present study, we investigated a role of GPR40 in the pathogenesis of fibrosarcoma HT1080 cells. The GPR40 gene expression was detected in HT1080 cells, but not the GPR120 gene. The cell motile and invasive activities were markedly enhanced by GPR40 knockdown, compared with control cells. To evaluate whether GPR40 is involved in the cellular functions of HT1080 cells during anticancer drug treatment, HT1080 cells were maintained in condition medium containing cisplatin (CDDP) (0.01–1.0 μM) for 6 mo. The expression levels of the GPR40 gene was elevated by the long‐term CDDP treatment in HT1080 cells, while the GPR120 gene expression remained unchanged. The cell motile and invasive activities of HT1080 cells treated with CDDP were significantly lower than those of untreated cells. In gelatin zymography, the activities of matrix metalloproteinase‐2 (MMP‐2) and MMP‐9 of HT1080 cells were enhanced by the long‐term CDDP treatment. In addition, GW9508 which is an agonist of GPR40 and GPR120 suppressed the cell motile and invasive activities of HT1080 cells treated with CDDP as well as the MMP activation. These results suggest that GPR40 negatively regulates the tumor progression of fibrosarcoma cells. © 2015 Wiley Periodicals, Inc.