Sphingosine 1-phosphate and cancer

Nigel J. Pyne, Ashref El Buri, David Roger Adams, Susan Pyne

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The bioactive lipid, sphingosine 1-phosphate (S1P) is produced by phosphorylation of sphingosine and this is catalysed by two sphingosine kinase isoforms (SK1 and SK2). Here we discuss structural functional aspects of SK1 (which is a dimeric quaternary enzyme) that relate to coordinated coupling of membrane association with phosphorylation of Ser225 in the 'so-called' R-loop, catalytic activity and protein-protein interactions (e.g. TRAF2, PP2A and Gq). S1P formed by SK1 at the plasma-membrane is released from cells via S1P transporters to act on S1P receptors to promote tumorigenesis. We discuss here an additional novel mechanism that can operate between cancer cells and fibroblasts and which involves the release of the S1P receptor, S1P2 in exosomes from breast cancer cells that regulates ERK-1/2 signalling in fibroblasts. This novel mechanism of signalling might provide an explanation for the role of S1P2 in promoting metastasis of cancer cells and which is dependent on the micro-environmental niche.

Original languageEnglish
Pages (from-to)97-106
Number of pages10
JournalAdvances in Biological Regulation
Volume68
Early online date15 Sep 2017
DOIs
Publication statusPublished - May 2018

Keywords

  • Cancer cell-fibroblast interactions
  • Metastasis
  • Sphingosine 1-phosphate
  • Sphingosine 1-phosphate receptors
  • Sphingosine kinase

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Cancer Research

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