Diverse effects of G-protein-coupled free fatty acid receptors on the regulation of cellular functions in lung cancer cells

• Published in: Experimental cell research Vol. 342; no. 2; pp. 193 - 199
• Main Authors: Kita, Tsubasa, Kadochi, Yui, Takahashi, Kaede, Fukushima, Kaori, Yamasaki, Eri, Uemoto, Taiki, Hirane, Miku, Fukushima, Nobuyuki, Honoki, Kanya, Tsujiuchi, Toshifumi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.03.2016; Elsevier BV
• Subjects: Animals; Antineoplastic Agents - pharmacology; Benzoates - pharmacology; Cell Line, Tumor; Cell motility; Cell Movement; Cell Proliferation; Cellular biology; Cisplatin - pharmacology; Endothelial Cells - metabolism; Fatty acids; Gene Knockdown Techniques; GPR120; GPR40; Humans; Invasion; Lung cancer; Matrix Metalloproteinase 2 - metabolism; Methylamines - pharmacology; Mice; Propionates - pharmacology; Proteins; Pyrimidines - pharmacology; Rats; Receptors, G-Protein-Coupled - agonists; Receptors, G-Protein-Coupled - antagonists & inhibitors; Receptors, G-Protein-Coupled - physiology; Cell motility; GPR120; GPR40; Lung cancer; Invasion
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2016.03.008

Free fatty acids (FFAs) are dietary nutrients which mediate a variety of biological effects through binding to G-protein-coupled FFA receptors (FFARs). G-protein-coupled receptor 120 (GPR120) and GPR40 are identified as FFARs for long- and medium-chain fatty acids. Here we investigated whether GPR120 and GPR40 are involved in the acquisition of malignant properties in lung cancer cells. Three lung cancer RLCNR, LL/2 and A549 cells used in this study expressed GPR120 and GPR40 genes. The cell motile activities of all cells were significantly suppressed by a GPR40 antagonist GW1100. In addition, GPR40 knockdown inhibited the cell motile activity of A549 cells. In gelatin zymography, matrix metalloproteinase-2 (MMP-2) activity in GPR40 knockdown was significantly lower than that in control cells. Next, to evaluate effects of GPR120 and GPR40 on cellular functions induced by anti-cancer drug, the long-term cisplatin (CDDP) treated (A549-CDDP) cells were generated. The expression levels of GPR120 and GPR40 were significantly decreased in A549-CDDP cells. While A549-CDDP cells showed the high cell motile activity, GW1100 suppressed the cell motile activity of A549-CDDP cells. These results demonstrate that GPR120 negatively and GPR40 positively regulate cellular functions during tumor progression in lung cancer cells. •GPR120 inhibited and GPR40 stimulate cell motile activity of human lung cancer cells.•The cell motile activity of lung cancer cells is suppressed by GPR40 knockdown.•MMP activation and angiogenesis are regulated by GPR120 and GPR40 in lung cancer cells.•GPR120 and GPR40 expressions were decreased in the long-term cisplatin treated cells.•GPR120 and GPR40 are involved in the regulation of cellular functions in lung cancer cells.