title: Choline-releasing glycerophosphodiesterase EDI3 links the tumor metabolome to signaling network activities.
abstract: Recently, EDI3 was identified as a key factor for choline metabolism that controls tumor cell migration and is associated with metastasis in endometrial carcinomas. EDI3 cleaves glycerophosphocholine (GPC) to form choline and glycerol-3-phosphate (G3P). Choline is then further metabolized to phosphatidylcholine (PtdC), the major lipid in membranes and a key player in membrane-mediated cell signaling. The second product, G3P, is a precursor molecule for several lipids with central roles in signaling, for example lysophosphatidic acid (LPA), phosphatidic acid (PA) and diacylglycerol (DAG). LPA activates intracellular signaling pathways by binding to specific LPA receptors, including membrane-bound G protein-coupled receptors and the intracellular nuclear receptor, PPARγ. Conversely, PA and DAG mediate signaling by acting as lipid anchors that bind and activate several signaling proteins. For example, binding of GTPases and PKC to PA and DAG, respectively, increases the activation of signaling networks, mediating processes such as migration, adhesion, proliferation or anti-apoptosis-all relevant for tumor development. We present a concept by which EDI3 either directly generates signaling molecules or provides "membrane anchors" for downstream signaling factors. As a result, EDI3 links choline metabolism to signaling activities resulting in a more malignant phenotype.
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors at the University of Dortmund (IfADo), Dortmund, Germany. marchan@ifado.de
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Marchan
authors.forename: Michaela S
authors.initials: MS
authors.lastname: Lesjak
authors.forename: Joanna D
authors.initials: JD
authors.lastname: Stewart
authors.forename: Roland
authors.initials: R
authors.lastname: Winter
authors.forename: Janine
authors.initials: J
authors.lastname: Seeliger
authors.forename: Jan G
authors.initials: JG
authors.lastname: Hengstler
mesh_terms: D000818:Animals; D002794:Choline / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000201:enzymology* / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: C011439:1,2-diacylglycerol; D004075:Diglycerides; D008246:Lysophospholipids; D010712:Phosphatidic Acids; D010727:Phosphoric Diester Hydrolases; C038133:glycerophosphodiester phosphodiesterase; D002794:Choline; C032881:lysophosphatidic acid