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Sphingolipids in Disease pp 3–27Cite as

Sphingosine Kinase/Sphingosine 1-Phosphate Signaling in Cancer Therapeutics and Drug Resistance

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 216))

Abstract

In this chapter, roles of bioactive sphingolipids, specifically sphingosine kinase 1 (SK1) and 2 (SK2) and their product—sphingosine 1-phosphate (S1P)—will be reviewed with respect to regulation of cancer growth, metastasis, chemotherapeutics, and drug resistance. Sphingolipids are known to be key bioeffector molecules that regulate cancer proliferation, angiogenesis, and cell death. Sphingolipid molecules such as ceramide and S1P have been shown to control cancer cell death and proliferation, respectively. Roles of S1P have been described with respect to their intracellular and extracellular pro-survival and drug resistance functions mostly through S1P receptor (S1PR1-5) engagement. Identification of novel intracellular SK/S1P targets has broadened the existing complex regulatory roles of bioactive sphingolipids in cancer pathogenesis and therapeutics. Thus, deciphering the biochemical and molecular regulation of SK/S1P/S1PR signaling could permit development of novel therapeutic interventions to improve cancer therapy and/or overcome drug resistance.

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Acknowledgments

We thank the members of the Ogretmen laboratory for their helpful discussions and apologize to those investigators whose important work was not included in this chapter because of space limitations. BO is funded by research grants from the National Institutes of Health. We thank Dr. Jennifer Schnellmann for her editorial review.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 86, Jonathan Lucas Street, Room 512A, Charleston, SC, 29425, USA

    Shanmugam Panneer Selvam & Besim Ogretmen

  2. Hollings Cancer Center, Medical University of South Carolina, 86, Jonathan Lucas Street, Room 512A, Charleston, SC, 29425, USA

    Shanmugam Panneer Selvam & Besim Ogretmen

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  1. Shanmugam Panneer Selvam
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  2. Besim Ogretmen
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Correspondence to Besim Ogretmen .

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  1. , Department of Molecular Biology, University of Duisburg-Essen, Hufelandstraße 55, Essen, 45122, Germany

    Erich Gulbins

  2. Division of Pulmonary, Allergy, Critical, Department of Medicine, Indiana University School of Medicine, W. Walnut Street 980, Indianapolis, 46202, Indiana, USA

    Irina Petrache

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Selvam, S.P., Ogretmen, B. (2013). Sphingosine Kinase/Sphingosine 1-Phosphate Signaling in Cancer Therapeutics and Drug Resistance. In: Gulbins, E., Petrache, I. (eds) Sphingolipids in Disease. Handbook of Experimental Pharmacology, vol 216. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1511-4_1

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