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“Dicing and Splicing” Sphingosine Kinase and Relevance to Cancer

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 activi...

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Autores principales: Haddadi, Nahal, Lin, Yiguang, Simpson, Ann M., Nassif, Najah T., McGowan, Eileen M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618540/
https://www.ncbi.nlm.nih.gov/pubmed/28869494
http://dx.doi.org/10.3390/ijms18091891
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author Haddadi, Nahal
Lin, Yiguang
Simpson, Ann M.
Nassif, Najah T.
McGowan, Eileen M.
author_facet Haddadi, Nahal
Lin, Yiguang
Simpson, Ann M.
Nassif, Najah T.
McGowan, Eileen M.
author_sort Haddadi, Nahal
collection PubMed
description 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.
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spelling pubmed-56185402017-09-30 “Dicing and Splicing” Sphingosine Kinase and Relevance to Cancer Haddadi, Nahal Lin, Yiguang Simpson, Ann M. Nassif, Najah T. McGowan, Eileen M. Int J Mol Sci Review 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. MDPI 2017-09-02 /pmc/articles/PMC5618540/ /pubmed/28869494 http://dx.doi.org/10.3390/ijms18091891 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Haddadi, Nahal
Lin, Yiguang
Simpson, Ann M.
Nassif, Najah T.
McGowan, Eileen M.
“Dicing and Splicing” Sphingosine Kinase and Relevance to Cancer
title “Dicing and Splicing” Sphingosine Kinase and Relevance to Cancer
title_full “Dicing and Splicing” Sphingosine Kinase and Relevance to Cancer
title_fullStr “Dicing and Splicing” Sphingosine Kinase and Relevance to Cancer
title_full_unstemmed “Dicing and Splicing” Sphingosine Kinase and Relevance to Cancer
title_short “Dicing and Splicing” Sphingosine Kinase and Relevance to Cancer
title_sort “dicing and splicing” sphingosine kinase and relevance to cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618540/
https://www.ncbi.nlm.nih.gov/pubmed/28869494
http://dx.doi.org/10.3390/ijms18091891
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