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

Sathya Narayanan Patmanathan1, Steven P Johnson2, Sook Ling Lai1

  • 1Department of Oral Biology and Biomedical Sciences and Oral Cancer Research &Coordinating Centre, Faculty of Dentistry, University of Malaya, 50603, Kuala Lumpur, Malaysia.

Scientific Reports
|May 11, 2016
PubMed

Insights

Sphingosine 1-phosphate (S1P) signaling promotes oral squamous cell carcinoma (OSCC) aggressiveness. Targeting S1P pathways, like with FTY720, shows therapeutic potential against OSCC, enhancing chemotherapy effectiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Oral squamous cell carcinoma (OSCC) has a high mortality rate, necessitating novel therapeutic targets.
  • Current molecular targeted therapies are not standard for OSCC treatment.
  • Previous data suggests dysregulation of sphingosine 1-phosphate (S1P) metabolism and signaling in OSCC.

Purpose of the Study:

  • To investigate the role of S1P signaling in the pathogenesis of OSCC.
  • To identify S1P signaling as a potential therapeutic target for OSCC.

Main Methods:

  • Analysis of SPHK1 and SGPL1 mRNA expression in OSCC tissues.
  • In vitro studies using OSCC cell lines to assess S1P effects on migration, invasion, and cisplatin-induced apoptosis.
  • Evaluation of S1P receptor expression in primary OSCC.
  • Assessment of FTY720's effect on OSCC cell apoptosis and its synergy with cisplatin.

Main Results:

  • SPHK1 was upregulated, and low SGPL1 mRNA levels correlated with worse survival in OSCC.
  • S1P enhanced OSCC cell migration/invasion and reduced cisplatin-induced cell death.
  • S1PR2 was over-expressed in a subset of OSCC tumors and mediated S1P-induced migration.
  • FTY720 induced apoptosis in OSCC cells and synergized with cisplatin to enhance cell death.

Conclusions:

  • S1P signaling significantly contributes to OSCC aggressiveness by promoting migration, invasion, and chemoresistance.
  • S1P signaling represents a promising therapeutic target for OSCC.
  • FTY720 demonstrates potential as an anti-OSCC agent, particularly in combination with cisplatin.

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