Involvement of FFA1 and FFA4 in the regulation of cellular functions during tumor progression in colon cancer cells

• Published in: Experimental cell research 2018-08, Vol.369 (1), p.54-60
• Main Authors: Takahashi, Kaede, Fukushima, Kaori, Onishi, Yuka, Minami, Kanako, Otagaki, Shiho, Ishimoto, Kaichi, Fukushima, Nobuyuki, Honoki, Kanya, Tsujiuchi, Toshifumi
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ANTINEOPLASTIC DRUGS; CARBOXYLIC ACIDS; Cisplatin; Colon cancer cells; COLONY FORMATION; FFA1; FFA4; Fluorouracil; FLUOROURACILS; LARGE INTESTINE; NEOPLASMS
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2018.05.005

Free fatty acid receptor 1 (FFA1) and FFA4 mediate a variety of biological responses through binding of medium- and long-chain free fatty acids. The aim of this study was to investigate an involvement of FFA1 and FFA4 in the regulation of cellular functions during tumor progression in colon cancer cells. The long-term fluorouracil (5-FU) and cisplatin (CDDP) treated cells were generated from DLD1 cells (DLD-5FU and DLD-CDDP cells, respectively). FFAR1 expressions were lower in DLD-5FU and DLD-CDDP cells than in DLD1 cells. In contrast, DLD-5FU and DLD-CDDP cells showed the high FFAR4 expressions, compared with DLD1 cells. The cell motile activities of DLD-5FU and DLD-CDDP cells were reduced by GW9508 which is an agonist of FFA1 and FFA4. Moreover, GW1100, an antagonist of FFA1, inhibited the cell motile activities of DLD-5FU and DLD-CDDP cells. To evaluate whether FFA1 and FFA4 regulate the enhancement of cell motility, invasion and colony formation, highly migratory (hmDLD1) cells were established from DLD1 cells. FFAR1 expression was significantly higher in hmDLD1 cells than in DLD1 cells, but no change of FFAR4 expression was observed. The elevated cell motile and invasive activities and colony formation of hmDLD1 cells were suppressed by FFA1 inhibition. These results suggest that FFA1 and FFA4 are involved in the regulation of cellular functions during tumor progression in colon cancer DLD1 cells. •FFAR1 and FFAR4 expressions are changed by anticancer drugs in colon cancer cells.•FFA1 stimulates and FFA4 inhibits cellular functions of DLD1 cells.•FFAR1 expression is markedly elevated in highly migratory DLD1 cells.•Cell migration and colony formation of DLD1 cells are suppressed by FFA1 inhibition.•FFA1 and FFA4 regulate cellular functions during tumor progression in DLD1 cells.