1. LPA Is a Chemorepellent for B16 Melanoma Cells: Action through the cAMP-Elevating LPA5 Receptor
- Author
-
Elisa Matas-Rico, Adrian Rzadkowski, Wouter H. Moolenaar, Maikel Jongsma, and Kees Jalink
- Subjects
Serum ,Melanoma, Experimental ,lcsh:Medicine ,Signal transduction ,Biochemistry ,Mice ,chemistry.chemical_compound ,Molecular cell biology ,Phosphatidylinositol Phosphates ,Sphingosine ,Lysophosphatidic acid ,Cyclic AMP ,Signaling in Cellular Processes ,Membrane Receptor Signaling ,Polylysine ,Receptors, Lysophosphatidic Acid ,lcsh:Science ,Extracellular Signal-Regulated MAP Kinases ,Receptor ,Multidisciplinary ,Chemotaxis ,Mechanisms of Signal Transduction ,Signaling cascades ,Cell Polarity ,Cell migration ,Signaling in Selected Disciplines ,Lipids ,PKA signaling cascade ,Cell biology ,Cell Motility ,lipids (amino acids, peptides, and proteins) ,biological phenomena, cell phenomena, and immunity ,Cell Movement Signaling ,Intracellular ,Research Article ,Subcellular Fractions ,Adenylyl Cyclase Signaling Pathway ,Biophysics ,Biology ,Transfection ,Signaling Pathways ,Lipid Mediators ,Chemorepulsion ,Growth Factors ,Animals ,Humans ,Protein kinase A ,Cell Proliferation ,G protein-coupled receptor ,Oncogenic Signaling ,Phosphoric Diester Hydrolases ,lcsh:R ,Cell Membrane ,Proteins ,Lipid signaling ,Cyclic AMP-Dependent Protein Kinases ,Molecular biology ,G-Protein Signaling ,chemistry ,alpha-MSH ,lcsh:Q ,Lysophospholipids ,HeLa Cells - Abstract
Lysophosphatidic acid (LPA), a lipid mediator enriched in serum, stimulates cell migration, proliferation and other functions in many cell types. LPA acts on six known G protein-coupled receptors, termed LPA(1-6), showing both overlapping and distinct signaling properties. Here we show that, unexpectedly, LPA and serum almost completely inhibit the transwell migration of B16 melanoma cells, with alkyl-LPA(18:1) being 10-fold more potent than acyl-LPA(18:1). The anti-migratory response to LPA is highly polarized and dependent on protein kinase A (PKA) but not Rho kinase activity; it is associated with a rapid increase in intracellular cAMP levels and PIP3 depletion from the plasma membrane. B16 cells express LPA(2), LPA(5) and LPA(6) receptors. We show that LPA-induced chemorepulsion is mediated specifically by the alkyl-LPA-preferring LPA(5) receptor (GPR92), which raises intracellular cAMP via a noncanonical pathway. Our results define LPA(5) as an anti-migratory receptor and they implicate the cAMP-PKA pathway, along with reduced PIP3 signaling, as an effector of chemorepulsion in B16 melanoma cells.
- Published
- 2011
- Full Text
- View/download PDF