Targeting Sphingosine-1-Phosphate in Hematologic Malignancies

Author(s): Christina E. Stevenson, Kazuaki Takabe, Masayuki Nagahashi, Sheldon Milstien, Sarah Spiegel.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 11 , Issue 9 , 2011

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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

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Article Details

VOLUME: 11
ISSUE: 9
Year: 2011
Page: [794 - 798]
Pages: 5
DOI: 10.2174/187152011797655122
Price: $58

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