The role of sphingosine-1-phosphate in the epithelial to mesenchymal transition in cancer cells

  • Justin Colin Greig

Student thesis: Master's Thesis

Abstract

Sphingosine-1-Phosphate (S1P) is a bioactive lipid that has been shown to regulate hallmark cancer characteristics, one of which is Epithelial to Mesenchymal Transition (EMT). EMT is the mechanism by which an epithelial cell gains the motility to migrate throughout the body by shifting from a stationary epithelial phenotype to a migratory mesenchymal phenotype. The aim of this study was to investigate the role S1P plays in EMT, proliferation and migration in A549 lung epithelial carcinoma and PANC-1 pancreatic epithelial carcinoma cell lines. Changes in the expression of E-cadherin (an epithelial cell marker) and vimentin (amesenchymal cell marker) were difficult to detect, which compromised the aim to investigate the role for S1P. However, results revealed that S1P2, S1P3 and S1P4 receptors were functional within A549 cells. The phospho-p38 MAPK pathway was coupled to these receptors when activated selectively, particularly for S1P3, and activation of all three receptor types inhibited proliferation. S1P stimulation however, promoted migration of A549 cells. PANC-1 cells also had the unexpected presence of S1P4 receptors. Activation of S1P4 in these cells decreased proliferation but increased PANC-1 cell migration and phosphorylation of ERK-1/2 and p38MAPK. PANC-1 cells also contained functional S1P1 and S1P2 receptors that inhibited proliferation. Overall, a pharmacological approach demonstrated that S1P receptors regulate cancer cell proliferation, migration and signal pathways in a cell-specific manner.
Date of Award9 Jun 2020
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SupervisorSusan Pyne (Supervisor)

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