Lysophosphatidic acid (LPA) signaling via LPA4 and LPA6 negatively regulates cell motile activities of colon cancer cells.

Lysophosphatidic acid (LPA) is an extracellular biological lipid and interacts with six subtypes of G protein-coupled LPA receptors (LPA1 to LPA6). LPA receptors exhibit a variety of cellular functions, depending on types of cancer cells. In this study, to assess the roles of LPA4 and LPA6 in cell growth and motile activities of colon cancer cells, LPA4 and LPA6 knockdown cells were established from DLD1 and HCT116 cells. LPA treatment increased the cell growth activities of LPA4 and LPA6 knockdown cells, compared with control cells. The cell motile activities of LPA4 and LPA6 knockdown cells were significantly higher than those of control cells. To evaluate the effects of LPA4 and LPA6 on cell motile activity induced by anticancer drug, long-term fluorouracil (5-FU) treated (DLD-5FU) cells were generated. The expression levels of LPAR1, LPAR4 and LPAR6 genes were significantly increased in DLD-5FU cells. DLD-5FU cells showed the high cell motile activity, compared with DLD1 cells. The increased cell motile activity was markedly stimulated by LPA4 and LPA6 knockdown. In contrast, the cell motile activity enhanced by 5-FU treatment was suppressed by LPA1 knockdown. These results suggest that LPA signaling via LPA4 and LPA6 negatively regulates the cell motile activities of DLD1 and HCT116 cells as well as long-term 5-FU treated cells.