Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond

被引:364
作者
Kunkel, Gregory T. [1 ]
Maceyka, Michael [1 ]
Milstien, Sheldon [1 ]
Spiegel, Sarah [1 ]
机构
[1] Virginia Commonwealth Univ, Sch Med, Massey Canc Ctr, Dept Biochem & Mol Biol, Richmond, VA 23298 USA
基金
美国国家卫生研究院;
关键词
SPHINGOSINE KINASE 1; SIGNAL-REGULATED KINASE-1/2; PERSISTENT STAT3 ACTIVATION; 1-PHOSPHATE RECEPTORS; TRANSPORTER SPNS2; S1P(1) ANTAGONIST; LYMPHOCYTE TRAFFICKING; ENDOTHELIAL-CELLS; FTY720; INHIBITION;
D O I
10.1038/nrd4099
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The bioactive lipid sphingosine-1-phosphate (S1P) is involved in multiple cellular signalling systems and has a pivotal role in the control of immune cell trafficking. As such, S1P has been implicated in disorders such as cancer and inflammatory diseases. This Review discusses the ways in which S1P might be therapeutically targeted - for example, via the development of chemical inhibitors that target the generation, transport and degradation of S1P and via the development of specific S1P receptor agonists. We also highlight recent conflicting results observed in preclinical studies targeting S1P and discuss ongoing clinical trials in this field.
引用
收藏
页码:688 / 702
页数:15
相关论文
共 142 条
[1]  
Aguilar Ana, 2012, Adv Biol Regul, V52, P17
[2]   Sphingosine-1-phosphate Lyase Deficiency Produces a Pro-inflammatory Response While Impairing Neutrophil Trafficking [J].
Allende, Maria L. ;
Bektas, Meryem ;
Lee, Bridgin G. ;
Bonifacino, Eliana ;
Kang, Jiman ;
Tuymetova, Galina ;
Chen, WeiPing ;
Saba, Julie D. ;
Proia, Richard L. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (09) :7348-7358
[3]   Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2 [J].
Alvarez, Sergio E. ;
Harikumar, Kuzhuvelil B. ;
Hait, Nitai C. ;
Allegood, Jeremy ;
Strub, Graham M. ;
Kim, Eugene Y. ;
Maceyka, Michael ;
Jiang, Hualiang ;
Luo, Cheng ;
Kordula, Tomasz ;
Milstien, Sheldon ;
Spiegel, Sarah .
NATURE, 2010, 465 (7301) :1084-U149
[4]   Pharmacological inhibition of sphingosine kinase isoforms alters estrogen receptor signaling in human breast cancer [J].
Antoon, James W. ;
Meacham, William D. ;
Bratton, Melyssa R. ;
Slaughter, Evelyn M. ;
Rhodes, Lyndsay V. ;
Ashe, Hasina B. ;
Wiese, Thomas E. ;
Burow, Matthew E. ;
Beckman, Barbara S. .
JOURNAL OF MOLECULAR ENDOCRINOLOGY, 2011, 46 (03) :205-216
[5]   Antiestrogenic Effects of the Novel Sphingosine Kinase-2 Inhibitor ABC294640 [J].
Antoon, James W. ;
White, Martin D. ;
Meacham, William D. ;
Slaughter, Evelyn M. ;
Muir, Shannon E. ;
Elliott, Steven ;
Rhodes, Lyndsay V. ;
Ashe, Hasina B. ;
Wiese, Thomas E. ;
Smith, Charles D. ;
Burow, Matthew E. ;
Beckman, Barbara S. .
ENDOCRINOLOGY, 2010, 151 (11) :5124-5135
[6]   Chronic sphingosine 1-phosphate 1 receptor activation attenuates early-stage diabetic nephropathy independent of lymphocytes [J].
Awad, Alaa S. ;
Rouse, Michael D. ;
Khutsishvili, Konstantine ;
Huang, Liping ;
Bolton, W. Kline ;
Lynch, Kevin R. ;
Okusa, Mark D. .
KIDNEY INTERNATIONAL, 2011, 79 (10) :1090-1098
[7]   Inhibition of Sphingosine 1-Phosphate Lyase for the Treatment of Rheumatoid Arthritis: Discovery of (E)-1-(4((1R,2S,3R)-1,2,3,4-Tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone Oxime (LX2931) and (1R,2S,3R)-1-(2-(Isoxazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol (LX2932) [J].
Bagdanoff, Jeffrey T. ;
Donoviel, Michael S. ;
Nouraldeen, Amr ;
Carlsen, Marianne ;
Jessop, Theodore C. ;
Tarver, James ;
Aleem, Saadat ;
Dong, Li ;
Zhang, Haiming ;
Boteju, Lakmal ;
Hazelwood, Jill ;
Yan, Jack ;
Bednarz, Mark ;
Layek, Suman ;
Owusu, Iris B. ;
Gopinathan, Suma ;
Moran, Liam ;
Lai, Zhong ;
Kramer, Jeff ;
Kimball, S. David ;
Yalamanchili, Padmaja ;
Heydorn, William E. ;
Frazier, Kenny S. ;
Brooks, Barbara ;
Brown, Philip ;
Wilson, Alan ;
Sonnenburg, William K. ;
Main, Alan ;
Carson, Kenneth G. ;
Oravecz, Tamas ;
Augeri, David J. .
JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (24) :8650-8662
[8]   Genetic Sphingosine Kinase 1 Deficiency Significantly Decreases Synovial Inflammation and Joint Erosions in Murine TNF-α-Induced Arthritis [J].
Baker, DeAnna A. ;
Barth, Jeremy ;
Chang, Raymond ;
Obeid, Lina M. ;
Gilkeson, Gary S. .
JOURNAL OF IMMUNOLOGY, 2010, 185 (04) :2570-2579
[9]   S1P1 inhibits sprouting angiogenesis during vascular development [J].
Ben Shoham, Adi ;
Malkinson, Guy ;
Krief, Sharon ;
Shwartz, Yulia ;
Ely, Yona ;
Ferrara, Napoleone ;
Yaniv, Karina ;
Zelzer, Elazar .
DEVELOPMENT, 2012, 139 (20) :3859-3869
[10]   2-Imino-thiazolidin-4-one Derivatives as Potent, Orally Active S1P1 Receptor Agonists [J].
Bolli, Martin H. ;
Abele, Stefan ;
Binkert, Christoph ;
Bravo, Roberto ;
Buchmann, Stephan ;
Bur, Daniel ;
Gatfield, John ;
Hess, Patrick ;
Kohl, Christopher ;
Mangold, Celine ;
Mathys, Boris ;
Menyhart, Katalin ;
Mueller, Claus ;
Nayler, Oliver ;
Scherz, Michael ;
Schmidt, Gunther ;
Sippel, Virginie ;
Steiner, Beat ;
Strasser, Daniel ;
Treiber, Alexander ;
Weller, Thomas .
JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (10) :4198-4211