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Int. J. Mol. Sci. 2017, 18(9), 1891; doi:10.3390/ijms18091891

“Dicing and Splicing” Sphingosine Kinase and Relevance to Cancer

School of Life Sciences, Faculty of Science, University of Technology Sydney, 15 Broadway, Ultimo, Sydney, NSW 2007, Australia
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Received: 2 August 2017 / Revised: 29 August 2017 / Accepted: 29 August 2017 / Published: 2 September 2017
(This article belongs to the Special Issue Sphingolipids: Signals and Disease)
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Abstract

Sphingosine kinase (SphK) is a lipid enzyme that maintains cellular lipid homeostasis. Two SphK isozymes, SphK1 and SphK2, are expressed from different chromosomes and several variant isoforms are expressed from each of the isozymes, allowing for the multi-faceted biological diversity of SphK activity. Historically, SphK1 is mainly associated with oncogenicity, however in reality, both SphK1 and SphK2 isozymes possess oncogenic properties and are recognized therapeutic targets. The absence of mutations of SphK in various cancer types has led to the theory that cancer cells develop a dependency on SphK signaling (hyper-SphK signaling) or “non-oncogenic addiction”. Here we discuss additional theories of SphK cellular mislocation and aberrant “dicing and splicing” as contributors to cancer cell biology and as key determinants of the success or failure of SphK/S1P (sphingosine 1 phosphate) based therapeutics. View Full-Text
Keywords: sphingosine kinase (SphK); isozymes; variant isoforms; cancer therapy; sphingosine 1 phosphate (S1P) sphingosine kinase (SphK); isozymes; variant isoforms; cancer therapy; sphingosine 1 phosphate (S1P)
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Haddadi, N.; Lin, Y.; Simpson, A.M.; Nassif, N.T.; McGowan, E.M. “Dicing and Splicing” Sphingosine Kinase and Relevance to Cancer. Int. J. Mol. Sci. 2017, 18, 1891.

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