Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep25650
Title: Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2
Authors: Patmanathan, 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
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
FTY720 INDUCES APOPTOSIS
SPHINGOSINE 1-PHOSPHATE RECEPTORS
SQUAMOUS-CELL CARCINOMA
CANCER-CELLS
PROSTATE-CANCER
BREAST-CANCER
DOWN-REGULATION
TUMOR-GROWTH
SPHINGOSINE-1-PHOSPHATE
ACTIVATION
Issue Date: 10-May-2016
Publisher: NATURE PUBLISHING GROUP
Citation: Patmanathan, 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
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.
Source Title: SCIENTIFIC REPORTS
URI: https://scholarbank.nus.edu.sg/handle/10635/170347
ISSN: 20452322
DOI: 10.1038/srep25650
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
16. Aberrant expression of the S1P.pdfPublished version1.6 MBAdobe PDF

OPEN

PublishedView/Download

SCOPUSTM   
Citations

23
checked on Sep 19, 2020

Page view(s)

35
checked on Sep 17, 2020

Download(s)

1
checked on Sep 17, 2020

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.