Different roles of GPR120 and GPR40 in the acquisition of malignant properties in pancreatic cancer cells

• Published in: Biochemical and biophysical research communications 2015-09, Vol.465 (3), p.512-515
• Main Authors: Fukushima, Kaori, Yamasaki, Eri, Ishii, Shuhei, Tomimatsu, Ayaka, Takahashi, Kaede, Hirane, Miku, Fukushima, Nobuyuki, Honoki, Kanya, Tsujiuchi, Toshifumi
• Format: Article
• Language: English
• Subjects: Carcinogenesis; Cell Line, Tumor; Cell motility; Cell Movement; GPR120; GPR40; Humans; Invasion; Male; Neoplasm Invasiveness; Pancreatic cancer cells; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Receptors, G-Protein-Coupled - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.08.050

Free fatty acids (FFAs) act as extracellular signaling molecules through binding to G-protein-coupled FFA receptors (FFARs). GPR120 and GPR40 are identified as FFARs for medium- and long-chain fatty acids. In the present study, we investigated roles of GPR120 and GPR40 in cellular functions of pancreatic cancer PANC-1 cells, using GPR120 and GPR40 knockdown cells (PANC-sh120 and PANC-sh40 cells respectively). In cell motility assay, PANC-sh120 cells showed the low cell motility, compared with control cells. In contrast, the cell motility of PANC-sh40 cells was significantly higher than that of control cells. Activity levels of matrix metalloproteinases (MMPs) were measured by gelatin zymography. While PANC-sh120 cells indicated the reduced MMP-2 activity, MMP-2 activity in PANC-sh40 cells was significantly higher than that in control cells. On the other hand, no activation of MMP-9 was detected in all cells. In colony assay, the large sized colonies were markedly formed in PANC-sh40 cells. No colony formation was observed in PANC-sh120 cells as well as control cells. These results suggest that distinct effects of GPR120 and GPR40 are involved in the acquisition of malignant property in pancreatic cancer cells. •GPR120 stimulates cell motile activity of pancreatic cancer cells.•GPR40 suppresses cell motile activity of pancreatic cancer cells.•GPR120 knockdown reduces and GPP40 knockdown elevates invasive activity of PANC-1 cells.•GPR120 knockdown inhibits and GPP40 knockdown enhances tumorigenicity of PANC-1 cells.•Differential function of GPR120 and GPR40 regulates cellular responses of pancreatic cancer cells.