title: Unfolding the pathophysiological role of bioactive lysophospholipids.
abstract: Lysophospholipids (LPLs), including glycerol- and sphingoid-based lipids, stimulate cell signaling and play important pathophysiological roles in humans and other animals. These LPLs include lysophosphatidic acid (LPA), lysophosphatidylinositol (LPI), lysophosphatidylcholine (LPC), lysophosphatidylserine (LPS), sphingosine-1-phosphate (S1P), and sphingosylphosphorylcholine (SPC). Analyses of LPLs in human body fluids from subjects with different pathophysiological conditions reveal not only the relevance of LPLs in human diseases, but also their potential application as biomarkers and/or therapeutic targets. In recent years, the identification and/or characterization of the plasma membrane receptors for LPLs and enzymes regulating the metabolism of LPLs have greatly facilitated our understanding of their role and signaling properties. In vitro and in vivo functional and signaling studies have revealed the broad and potent biological effects of LPLs and the mechanisms of LPL actions in different cellular systems. Development of specific antagonists for each of the LPL receptors will provide powerful tools for dissecting signaling pathways mediated by receptor subtypes. More importantly, these antagonists may serve as therapeutics for relevant diseases. Genetic depletion of LPL receptors in mice has provided and will continue to provide critical information on the pathophysiological roles of LPL receptors. It is important to further evaluate the significance of targeting these bioactive LPL receptors, their downstream signaling molecules, and/or metabolic enzymes in the treatment of cancers and other diseases.
authors.affiliation: Department of Cancer Biology, The Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, OH 44195, USA. xuy@ccf.org
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Yi-Jin
authors.initials: YJ
authors.lastname: Xiao
authors.forename: Kui
authors.initials: K
authors.lastname: Zhu
authors.forename: Linnea M
authors.initials: LM
authors.lastname: Baudhuin
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Guiying
authors.initials: G
authors.lastname: Hong
authors.forename: Kwan-Sik
authors.initials: KS
authors.lastname: Kim
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Cristina
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.forename: Freager
authors.initials: F
authors.lastname: S  Williams
authors.forename: Paul
authors.initials: P
authors.lastname: Elson
authors.forename: Maurie
authors.initials: M
authors.lastname: Markman
authors.forename: Jerome
authors.initials: J
authors.lastname: Belinson
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000737:chemistry; D006801:Humans; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D015415:Biomarkers; D008246:Lysophospholipids