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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Targeting Sphingosine-1-Phosphate in Hematologic Malignancies

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

Volume 11 , Issue 9 , 2011

Page: [794 - 798] Pages: 5

DOI: 10.2174/187152011797655122

Price: $65


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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