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.
Keywords: Sphingosine-1-phosphate, sphingosine kinase, sphingosine-1-phosphate receptors, leukemia, lymphoma, hematologic malignancies, cytokines stimulate, GPCR, UDP-glucose, DLBCL, siRNA, DMS
Anti-Cancer Agents in Medicinal Chemistry
Title: Targeting Sphingosine-1-Phosphate in Hematologic Malignancies
Volume: 11 Issue: 9
Author(s): Christina E. Stevenson, Kazuaki Takabe, Masayuki Nagahashi, Sheldon Milstien and Sarah Spiegel
Affiliation:
Keywords: Sphingosine-1-phosphate, sphingosine kinase, sphingosine-1-phosphate receptors, leukemia, lymphoma, hematologic malignancies, cytokines stimulate, GPCR, UDP-glucose, DLBCL, siRNA, DMS
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.
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Cite this article as:
E. Stevenson Christina, Takabe Kazuaki, Nagahashi Masayuki, Milstien Sheldon and Spiegel Sarah, Targeting Sphingosine-1-Phosphate in Hematologic Malignancies, Anti-Cancer Agents in Medicinal Chemistry 2011; 11 (9) . https://dx.doi.org/10.2174/187152011797655122
DOI https://dx.doi.org/10.2174/187152011797655122 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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