Sphingosine 1-phosphate and cancer

Pyne, Nigel J. and El Buri, Ashref and Adams, David R. and Pyne, Susan (2018) Sphingosine 1-phosphate and cancer. Advances in Biological Regulation, 68. pp. 97-106. ISSN 2212-4934

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    Abstract

    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.

    Author(s):Pyne, Nigel J. ORCID logoORCID: https://orcid.org/0000-0002-5657-4578, El Buri, Ashref ORCID logoORCID: https://orcid.org/0000-0003-1681-0676, Adams, David R. and Pyne, Susan ORCID logoORCID: https://orcid.org/0000-0002-6608-9584
    Item type:Article
    ID code:61848
    Keywords:sphingosine 1-phosphate, sphingosine kinase, sphingosine 1-phosphate receptors, cancer cell-fibroblast interactions, metastasis, Pharmacy and materia medica, Neoplasms. Tumors. Oncology (including Cancer), Genetics, Molecular Biology, Molecular Medicine, Cancer Research
    Subjects:Medicine > Pharmacy and materia medica
    Medicine > Internal medicine > Neoplasms. Tumors. Oncology (including Cancer)
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:21 Sep 2017 16:33
    Last modified:28 Jan 2020 04:24
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/61848
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