title: Targeting sphingosine-1-phosphate in hematologic malignancies.
abstract: Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid mediator that regulates several processes important for hematologic cancer progression. S1P is generated by two sphingosine kinases, SphK1 and SphK2, and is exported outside the cell, where it activates specific cell surface S1P G-protein coupled receptors in autocrine/paracrine manner, coined "inside-out signaling". In this review, we highlight the importance of SphK1 and inside-out signaling by S1P in hematologic malignancy. We also summarize the results of studies targeting the SphK1/S1P/S1P receptor axis and the effects of the S1P receptor modulator, FTY720, in hematologic malignancy.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, 23298-0614, USA.
authors.forename: Christina E
authors.initials: CE
authors.lastname: Stevenson
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Takabe
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nagahashi
authors.forename: Sheldon
authors.initials: S
authors.lastname: Milstien
authors.forename: Sarah
authors.initials: S
authors.lastname: Spiegel
mesh_terms: D000818:Animals; D000068876:Fingolimod Hydrochloride; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008246:Lysophospholipids / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011409:Propylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D000099157:Sphingosine Kinase
chemical_list: D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate