Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond
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TLDR
The ways in which S1P might be therapeutically targeted are discussed — for example, via the development of chemical inhibitors that target the generation, transport and degradation of S 1P and via thedevelopment of specific S1p receptor agonists.Abstract:
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.read more
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References
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Journal ArticleDOI
The sphingolipid transporter spns2 functions in migration of zebrafish myocardial precursors.
TL;DR: It is shown that the export of S1P from cells requires Spns2, and the introduction of spns2 mRNA in the YSL restored the cardiac defect in the ko157 mutant, thereby regulating myocardial precursor migration.
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Sphingolipid Metabolism Cooperates with BAK and BAX to Promote the Mitochondrial Pathway of Apoptosis
Jerry E. Chipuk,Gavin P. McStay,Archana Bharti,Tomomi Kuwana,Christopher J. Clarke,Leah J. Siskind,Leah J. Siskind,Lina M. Obeid,Lina M. Obeid,Douglas R. Green +9 more
TL;DR: The studies suggest that BAK/BAX activation and apoptosis are coordinated through BH3-only proteins and a specific lipid milieu that is maintained by heterotypic membrane-mitochondrial interactions.
Journal ArticleDOI
STAT3-induced S1PR1 expression is crucial for persistent STAT3 activation in tumors
Heehyoung Lee,Jiehui Deng,Maciej Kujawski,Chunmei Yang,Yong-Yong Liu,Andreas Herrmann,Marcin Kortylewski,David Horne,G. Somlo,Stephen J. Forman,Richard Jove,Hua Yu +11 more
TL;DR: It is shown that STAT3-induced S1pr1 expression, as well as the S1P-S1PR1 pathway reciprocal regulation of STAT3 activity, is a major positive feedback loop for persistent STAT3 activation in cancer cells and the tumor microenvironment and for malignant progression.
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FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome–positive acute lymphocytic leukemia
Paolo Neviani,Ramasamy Santhanam,Joshua J. Oaks,Anna M. Eiring,Mario Notari,Bradley W. Blaser,Shujun Liu,Rossana Trotta,Natarajan Muthusamy,Carlo Gambacorti-Passerini,Brian J. Druker,Jorge E. Cortes,Guido Marcucci,Ching-Shih Chen,Nicole M. Verrills,Denis C. Roy,Michael A. Caligiuri,Clara D. Bloomfield,John C. Byrd,Danilo Perrotti +19 more
TL;DR: The data indicate that FTY720 induces apoptosis and impairs clonogenicity of imatinib/dasatinib-sensitive and -resistant p210/p190(BCR/ABL) myeloid and lymphoid cell lines and CML-BC and Ph1 ALL progenitors but not of normal CD34+ andCD34+/CD19+ bone marrow cells.
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Targeting the correct HDAC(s) to treat cognitive disorders
Andre Fischer,Farahnaz Sananbenesi,Alison Mungenast,Alison Mungenast,Alison Mungenast,Li-Huei Tsai,Li-Huei Tsai,Li-Huei Tsai +7 more
TL;DR: The specific roles of each HDAC protein and the possible function of distinct histone modifications are discussed, in the hope that this knowledge will aid in the development of diagnostic tools and in designing more potent and specific treatment for neurological disorders targeting selective HDAC proteins.