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Sphingosine‐1‐phosphate‐lyase deficiency affects glucose metabolism in a way that abets oncogenesis
Sphingosine‐1‐phosphate (S1P), a bioactive signaling lipid, is involved in several vital processes, including cellular proliferation, survival and migration, as well as neovascularization and inflammation. Its critical role in the development and progression of cancer is well documented. The metabol...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580888/ https://www.ncbi.nlm.nih.gov/pubmed/35973936 http://dx.doi.org/10.1002/1878-0261.13300 |
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author | Afsar, Sumaiya Y. Alam, Shah Fernandez Gonzalez, Carina van Echten‐Deckert, Gerhild |
author_facet | Afsar, Sumaiya Y. Alam, Shah Fernandez Gonzalez, Carina van Echten‐Deckert, Gerhild |
author_sort | Afsar, Sumaiya Y. |
collection | PubMed |
description | Sphingosine‐1‐phosphate (S1P), a bioactive signaling lipid, is involved in several vital processes, including cellular proliferation, survival and migration, as well as neovascularization and inflammation. Its critical role in the development and progression of cancer is well documented. The metabolism of S1P, which exerts its effect mainly via five G protein‐coupled receptors (S1PR(1–5)), is tightly regulated. S1P‐lyase (SGPL1) irreversibly cleaves S1P in the final step of sphingolipid catabolism and exhibits remarkably decreased enzymatic activity in tumor samples. In this study, we used SGPL1‐deficient (Sgpl1 ( −/− )) mouse embryonic fibroblasts (MEFs) and investigated the impact of S1P on glucose metabolism. Accumulated S1P activates, via its receptors (S1PR(1–3)), hypoxia‐inducible factor 1 and stimulates the expression of proteins involved in glucose uptake and breakdown, indicating that Sgpl1 ( −/− ) cells, like cancer cells, prefer to convert glucose to lactate even in the presence of oxygen. Accordingly, their rate of proliferation is significantly increased. Activation of the Akt/mTOR pathway and hence down‐regulation of autophagy indicate that these changes do not negatively affect the cellular energy status. In summary, we report on a newly identified role of the S1P/S1PR(1–3) axis in glucose metabolism in SGPL1‐deficient MEFs. |
format | Online Article Text |
id | pubmed-9580888 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95808882022-10-20 Sphingosine‐1‐phosphate‐lyase deficiency affects glucose metabolism in a way that abets oncogenesis Afsar, Sumaiya Y. Alam, Shah Fernandez Gonzalez, Carina van Echten‐Deckert, Gerhild Mol Oncol Research Articles Sphingosine‐1‐phosphate (S1P), a bioactive signaling lipid, is involved in several vital processes, including cellular proliferation, survival and migration, as well as neovascularization and inflammation. Its critical role in the development and progression of cancer is well documented. The metabolism of S1P, which exerts its effect mainly via five G protein‐coupled receptors (S1PR(1–5)), is tightly regulated. S1P‐lyase (SGPL1) irreversibly cleaves S1P in the final step of sphingolipid catabolism and exhibits remarkably decreased enzymatic activity in tumor samples. In this study, we used SGPL1‐deficient (Sgpl1 ( −/− )) mouse embryonic fibroblasts (MEFs) and investigated the impact of S1P on glucose metabolism. Accumulated S1P activates, via its receptors (S1PR(1–3)), hypoxia‐inducible factor 1 and stimulates the expression of proteins involved in glucose uptake and breakdown, indicating that Sgpl1 ( −/− ) cells, like cancer cells, prefer to convert glucose to lactate even in the presence of oxygen. Accordingly, their rate of proliferation is significantly increased. Activation of the Akt/mTOR pathway and hence down‐regulation of autophagy indicate that these changes do not negatively affect the cellular energy status. In summary, we report on a newly identified role of the S1P/S1PR(1–3) axis in glucose metabolism in SGPL1‐deficient MEFs. John Wiley and Sons Inc. 2022-08-16 2022-10 /pmc/articles/PMC9580888/ /pubmed/35973936 http://dx.doi.org/10.1002/1878-0261.13300 Text en © 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Afsar, Sumaiya Y. Alam, Shah Fernandez Gonzalez, Carina van Echten‐Deckert, Gerhild Sphingosine‐1‐phosphate‐lyase deficiency affects glucose metabolism in a way that abets oncogenesis |
title | Sphingosine‐1‐phosphate‐lyase deficiency affects glucose metabolism in a way that abets oncogenesis |
title_full | Sphingosine‐1‐phosphate‐lyase deficiency affects glucose metabolism in a way that abets oncogenesis |
title_fullStr | Sphingosine‐1‐phosphate‐lyase deficiency affects glucose metabolism in a way that abets oncogenesis |
title_full_unstemmed | Sphingosine‐1‐phosphate‐lyase deficiency affects glucose metabolism in a way that abets oncogenesis |
title_short | Sphingosine‐1‐phosphate‐lyase deficiency affects glucose metabolism in a way that abets oncogenesis |
title_sort | sphingosine‐1‐phosphate‐lyase deficiency affects glucose metabolism in a way that abets oncogenesis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580888/ https://www.ncbi.nlm.nih.gov/pubmed/35973936 http://dx.doi.org/10.1002/1878-0261.13300 |
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