An oncogenic role for sphingosine kinase 2

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dc.contributor.authorNeubauer, H.A.
dc.contributor.authorPham, D.H.
dc.contributor.authorZebol, J.R.
dc.contributor.authorMoretti, P.A.B.
dc.contributor.authorPeterson, A.L.
dc.contributor.authorLeclercq, T.M.
dc.contributor.authorChan, H.
dc.contributor.authorPowell, J.A.
dc.contributor.authorPitman, M.R.
dc.contributor.authorSamuel, M.S.
dc.contributor.authorBonder, C.S.
dc.contributor.authorCreek, D.J.
dc.contributor.authorGliddon, B.L.
dc.contributor.authorPitson, S.M.
dc.date.issued2016
dc.description.abstractWhile both human sphingosine kinases (SK1 and SK2) catalyze the generation of the pleiotropic signaling lipid sphingosine 1-phosphate, these enzymes appear to be functionally distinct. SK1 has well described roles in promoting cell survival, proliferation and neoplastic transformation. The roles of SK2, and its contribution to cancer, however, are much less clear. Some studies have suggested an antiproliferative/ pro-apoptotic function for SK2, while others indicate it has a prosurvival role and its inhibition can have anti-cancer effects. Our analysis of gene expression data revealed that SK2 is upregulated in many human cancers, but only to a small extent (up to 2.5-fold over normal tissue). Based on these findings, we examined the effect of different levels of cellular SK2 and showed that high-level overexpression reduced cell proliferation and survival, and increased cellular ceramide levels. In contrast, however, low-level SK2 overexpression promoted cell survival and proliferation, and induced neoplastic transformation in vivo. These findings coincided with decreased nuclear localization and increased plasma membrane localization of SK2, as well as increases in extracellular S1P formation. Hence, we have shown for the first time that SK2 can have a direct role in promoting oncogenesis, supporting the use of SK2-specific inhibitors as anti-cancer agents.
dc.description.statementofresponsibilityHeidi A. Neubauer, Duyen H. Pham, Julia R. Zebol, Paul A.B. Moretti, Amanda L. Peterson, Tamara M. Leclercq, Huasheng Chan, Jason A. Powell, Melissa R. Pitman, Michael S. Samuel, Claudine S. Bonder, Darren J. Creek, Briony L. Gliddon and Stuart M. Pitson
dc.identifier.citationOncotarget, 2016; 7(40):64886-64899
dc.identifier.doi10.18632/oncotarget.11714
dc.identifier.issn1949-2553
dc.identifier.issn1949-2553
dc.identifier.orcidNeubauer, H.A. [0000-0001-7372-7786]
dc.identifier.orcidPham, D.H. [0000-0003-0664-4133]
dc.identifier.orcidPitman, M.R. [0000-0002-9587-3837]
dc.identifier.orcidSamuel, M.S. [0000-0001-7880-6379]
dc.identifier.orcidBonder, C.S. [0000-0001-9875-967X]
dc.identifier.orcidPitson, S.M. [0000-0002-9527-2740]
dc.identifier.urihttp://hdl.handle.net/2440/103587
dc.language.isoen
dc.publisherImpact Journals
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/508098
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1042589
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1088855
dc.rightsCreative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License. PII: 11714
dc.source.urihttps://doi.org/10.18632/oncotarget.11714
dc.subjectsphingosine kinase 2; neoplastic transformation; oncogenesis; proliferation; tumorigenesis
dc.titleAn oncogenic role for sphingosine kinase 2
dc.typeJournal article
pubs.publication-statusPublished

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