Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep25650
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dc.titleAberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2
dc.contributor.authorPatmanathan, Sathya Narayanan
dc.contributor.authorJohnson, Steven P
dc.contributor.authorLai, Sook Ling
dc.contributor.authorBernam, Suthashini Panja
dc.contributor.authorLopes, Victor
dc.contributor.authorWei, Wenbin
dc.contributor.authorIbrahim, Maha Hafez
dc.contributor.authorTorta, Federico
dc.contributor.authorNarayanaswamy, Pradeep
dc.contributor.authorWenk, Markus R
dc.contributor.authorHerr, Deron R
dc.contributor.authorMurray, Paul G
dc.contributor.authorYap, Lee Fah
dc.contributor.authorPaterson, Ian C
dc.date.accessioned2020-06-18T03:27:57Z
dc.date.available2020-06-18T03:27:57Z
dc.date.issued2016-05-10
dc.identifier.citationPatmanathan, Sathya Narayanan, Johnson, Steven P, Lai, Sook Ling, Bernam, Suthashini Panja, Lopes, Victor, Wei, Wenbin, Ibrahim, Maha Hafez, Torta, Federico, Narayanaswamy, Pradeep, Wenk, Markus R, Herr, Deron R, Murray, Paul G, Yap, Lee Fah, Paterson, Ian C (2016-05-10). Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2. SCIENTIFIC REPORTS 6 (1). ScholarBank@NUS Repository. https://doi.org/10.1038/srep25650
dc.identifier.issn20452322
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/170347
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.
dc.language.isoen
dc.publisherNATURE PUBLISHING GROUP
dc.sourceElements
dc.subjectScience & Technology
dc.subjectMultidisciplinary Sciences
dc.subjectScience & Technology - Other Topics
dc.subjectFTY720 INDUCES APOPTOSIS
dc.subjectSPHINGOSINE 1-PHOSPHATE RECEPTORS
dc.subjectSQUAMOUS-CELL CARCINOMA
dc.subjectCANCER-CELLS
dc.subjectPROSTATE-CANCER
dc.subjectBREAST-CANCER
dc.subjectDOWN-REGULATION
dc.subjectTUMOR-GROWTH
dc.subjectSPHINGOSINE-1-PHOSPHATE
dc.subjectACTIVATION
dc.typeArticle
dc.date.updated2020-06-17T03:57:12Z
dc.contributor.departmentDEPT OF BIOCHEMISTRY
dc.contributor.departmentDEPT OF PHARMACOLOGY
dc.contributor.departmentLIFE SCIENCES INSTITUTE
dc.description.doi10.1038/srep25650
dc.description.sourcetitleSCIENTIFIC REPORTS
dc.description.volume6
dc.description.issue1
dc.description.placeUNITED KINGDOM
dc.published.statePublished
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