title: Lysophosphatidic acid (LPA) signaling via LPA4and LPA6negatively regulates cell motile activities of colon cancer cells.
abstract: Lysophosphatidic acid (LPA) is an extracellular biological lipid and interacts with six subtypes of G protein-coupled LPA receptors (LPA1to LPA6). LPA receptors exhibit a variety of cellular functions, depending on types of cancer cells. In this study, to assess the roles of LPA4and LPA6in cell growth and motile activities of colon cancer cells, LPA4and LPA6knockdown cells were established from DLD1 and HCT116 cells. LPA treatment increased the cell growth activities of LPA4and LPA6knockdown cells, compared with control cells. The cell motile activities of LPA4and LPA6knockdown cells were significantly higher than those of control cells. To evaluate the effects of LPA4and LPA6on 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 LPA4and LPA6knockdown. In contrast, the cell motile activity enhanced by 5-FU treatment was suppressed by LPA1knockdown. These results suggest that LPA signaling via LPA4and LPA6negatively regulates the cell motile activities of DLD1 and HCT116 cells as well as long-term 5-FU treated cells.
authors.affiliation: Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
authors.forename: Kaede
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Fukushima
authors.affiliation: Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Onishi
authors.affiliation: Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
authors.forename: Karin
authors.initials: K
authors.lastname: Inui
authors.affiliation: Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Node
authors.affiliation: Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Fukushima
authors.affiliation: Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Kanya
authors.initials: K
authors.lastname: Honoki
authors.affiliation: Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan. Electronic address: ttujiuch@life.kindai.ac.jp.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tsujiuchi
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D005472:Fluorouracil / Q000494:pharmacology; D045325:HCT116 Cells; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism* / Q000494:pharmacology; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000378:metabolism*; D018048:Receptors, Purinergic P2; D015398:Signal Transduction
chemical_list: D000964:Antimetabolites, Antineoplastic; C082320:LPAR4 protein, human; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D011983:Receptors, Purinergic; D018048:Receptors, Purinergic P2; C032881:lysophosphatidic acid; D005472:Fluorouracil
keywords: Cell motility; Colon cancer cells; Fluorouracil; LPA; LPA receptor