title: Sphingosine-1-phosphate-activated TRPC1 channel controls chemotaxis of glioblastoma cells.
abstract: TRP channels are involved in the control of a broad range of cellular functions such as cell proliferation and motility. We investigated the gating mechanism of TRPC1 channel and its role in U251 glioblastoma cells migration in response to chemotaxis by platelet-derived growth factor (PDGF). PDGF induced an influx of Ca2+that was partially inhibited after pretreatment of the cells with SKI-II, a specific inhibitor of sphingosine kinase producing sphingosine-1-P (S1P). S1P by itself also induced an entry of Ca2+. Interestingly, PDGF- and S1P-induced entries of Ca2+were lost in siRNA-TRPC1 treated cells. PDGF-induced chemotaxis of U251 cells was dramatically inhibited in cells treated with SKI-II. This effect was almost completely rescued by addition of synthetic S1P. Chemotaxis was also completely lost in siRNA-TRPC1 treated cells and interestingly, the rescue of migration of cells treated with SKI-II by S1P was dependent on the expression of TRPC1. Immunocytochemistry revealed that, in response to PDGF, TRPC1 translocated from inside of the cell to the front of migration (lamellipodes). This effect seemed PI3K dependent as it was inhibited by cell pre-treatment with LY294002, a PI3-kinase inhibitor. Our results thus identify S1P as a potential activator of TRPC1, a channel involved in cell orientation during chemotaxis by PDGF.
authors.affiliation: Université catholique de Louvain, Institute of Neuroscience, Laboratory of Cell Physiology, av. Mounier 53, box B1.53.17, 1200 Brussels, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lepannetier
authors.affiliation: Université catholique de Louvain, Institute of Neuroscience, Laboratory of Cell Physiology, av. Mounier 53, box B1.53.17, 1200 Brussels, Belgium.
authors.forename: Nadège
authors.initials: N
authors.lastname: Zanou
authors.affiliation: Université catholique de Louvain, Institute of Neuroscience, Laboratory of Cell Physiology, av. Mounier 53, box B1.53.17, 1200 Brussels, Belgium.
authors.forename: Xavier
authors.initials: X
authors.lastname: Yerna
authors.affiliation: Université catholique de Louvain, Institute of Neuroscience, Laboratory of Cell Physiology, av. Mounier 53, box B1.53.17, 1200 Brussels, Belgium.
authors.forename: Noémie
authors.initials: N
authors.lastname: Emeriau
authors.affiliation: Université catholique de Louvain, Institute of Neuroscience, Laboratory of Cell Physiology, av. Mounier 53, box B1.53.17, 1200 Brussels, Belgium.
authors.forename: Inès
authors.initials: I
authors.lastname: Dufour
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, av. Mounier 72, box B1.72.01, 1200 Brussels, Belgium.
authors.forename: Julien
authors.initials: J
authors.lastname: Masquelier
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, av. Mounier 72, box B1.72.01, 1200 Brussels, Belgium.
authors.forename: Giulio
authors.initials: G
authors.lastname: Muccioli
authors.affiliation: Université catholique de Louvain, Institute of Neuroscience, Laboratory of Cell Physiology, av. Mounier 53, box B1.53.17, 1200 Brussels, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tajeddine
authors.affiliation: Université catholique de Louvain, Institute of Neuroscience, Laboratory of Cell Physiology, av. Mounier 53, box B1.53.17, 1200 Brussels, Belgium. Electronic address: philippe.gailly@uclouvain.be.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gailly
mesh_terms: D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects*; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D050052:TRPC Cation Channels / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D008246:Lysophospholipids; D010982:Platelet-Derived Growth Factor; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; C060506:sphingosine 1-phosphate; D013110:Sphingosine; D002118:Calcium
keywords: Astrocytoma; Calcium; Cancer; Cell migration; Lipids; TRP channels