Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2.

2.50
Hdl Handle:
http://hdl.handle.net/11287/609183
Title:
Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2.
Authors:
Patmanathan, S. N.; Johnson, Steven P.; Lai, Sook L.; Panja Bernam, S.; Lopes, V.; Wei, W.; Ibrahim, M. H.; Torta, F.; Narayanaswamy, P.; Wenk, M. R.; Herr, D. R.; Murray, P. G.; Yap, L. F.; Paterson, I. C.
Abstract:
Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target.
Citation:
Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2. 2016, 6:25650 Sci Rep
Publisher:
Nature
Journal:
Scientific reports
Issue Date:
10-May-2016
URI:
http://hdl.handle.net/11287/609183
DOI:
10.1038/srep25650
PubMed ID:
27160553
Additional Links:
http://www.nature.com/articles/srep25650
Note:
This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.
Type:
Journal Article
Language:
en
ISSN:
2045-2322
Appears in Collections:
Molecular Genetics; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorPatmanathan, S. N.en
dc.contributor.authorJohnson, Steven P.en
dc.contributor.authorLai, Sook L.en
dc.contributor.authorPanja Bernam, S.en
dc.contributor.authorLopes, V.en
dc.contributor.authorWei, W.en
dc.contributor.authorIbrahim, M. H.en
dc.contributor.authorTorta, F.en
dc.contributor.authorNarayanaswamy, P.en
dc.contributor.authorWenk, M. R.en
dc.contributor.authorHerr, D. R.en
dc.contributor.authorMurray, P. G.en
dc.contributor.authorYap, L. F.en
dc.contributor.authorPaterson, I. C.en
dc.date.accessioned2016-05-12T13:18:29Zen
dc.date.available2016-05-12T13:18:29Zen
dc.date.issued2016-05-10en
dc.identifier.citationAberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2. 2016, 6:25650 Sci Repen
dc.identifier.issn2045-2322en
dc.identifier.pmid27160553en
dc.identifier.doi10.1038/srep25650en
dc.identifier.urihttp://hdl.handle.net/11287/609183en
dc.description.abstractOral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target.en
dc.language.isoenen
dc.publisherNatureen
dc.relation.urlhttp://www.nature.com/articles/srep25650en
dc.rightsArchived with thanks to Scientific Reports. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/en
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleAberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2.en
dc.typeJournal Articleen
dc.identifier.journalScientific reportsen
dc.description.noteThis article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.en
dc.type.versionPublisheden

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