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FABP5 coordinates lipid signaling that promotes prostate cancer metastasis
Prostate cancer (PCa) is defined by dysregulated lipid signaling and is characterized by upregulation of lipid metabolism-related genes including fatty acid binding protein 5 (FABP5), fatty acid synthase (FASN), and monoacylglycerol lipase (MAGL). FASN and MAGL are enzymes that generate cellular fat...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908725/ https://www.ncbi.nlm.nih.gov/pubmed/31831821 http://dx.doi.org/10.1038/s41598-019-55418-x |
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author | Carbonetti, Gregory Wilpshaar, Tessa Kroonen, Jessie Studholme, Keith Converso, Cynthia d’Oelsnitz, Simon Kaczocha, Martin |
author_facet | Carbonetti, Gregory Wilpshaar, Tessa Kroonen, Jessie Studholme, Keith Converso, Cynthia d’Oelsnitz, Simon Kaczocha, Martin |
author_sort | Carbonetti, Gregory |
collection | PubMed |
description | Prostate cancer (PCa) is defined by dysregulated lipid signaling and is characterized by upregulation of lipid metabolism-related genes including fatty acid binding protein 5 (FABP5), fatty acid synthase (FASN), and monoacylglycerol lipase (MAGL). FASN and MAGL are enzymes that generate cellular fatty acid pools while FABP5 is an intracellular chaperone that delivers fatty acids to nuclear receptors to enhance PCa metastasis. Since FABP5, FASN, and MAGL have been independently implicated in PCa progression, we hypothesized that FABP5 represents a central mechanism linking cytosolic lipid metabolism to pro-metastatic nuclear receptor signaling. Here, we show that the abilities of FASN and MAGL to promote nuclear receptor activation and PCa metastasis are critically dependent upon co-expression of FABP5 in vitro and in vivo. Our findings position FABP5 as a key driver of lipid-mediated metastasis and suggest that disruption of lipid signaling via FABP5 inhibition may constitute a new avenue to treat metastatic PCa. |
format | Online Article Text |
id | pubmed-6908725 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69087252019-12-16 FABP5 coordinates lipid signaling that promotes prostate cancer metastasis Carbonetti, Gregory Wilpshaar, Tessa Kroonen, Jessie Studholme, Keith Converso, Cynthia d’Oelsnitz, Simon Kaczocha, Martin Sci Rep Article Prostate cancer (PCa) is defined by dysregulated lipid signaling and is characterized by upregulation of lipid metabolism-related genes including fatty acid binding protein 5 (FABP5), fatty acid synthase (FASN), and monoacylglycerol lipase (MAGL). FASN and MAGL are enzymes that generate cellular fatty acid pools while FABP5 is an intracellular chaperone that delivers fatty acids to nuclear receptors to enhance PCa metastasis. Since FABP5, FASN, and MAGL have been independently implicated in PCa progression, we hypothesized that FABP5 represents a central mechanism linking cytosolic lipid metabolism to pro-metastatic nuclear receptor signaling. Here, we show that the abilities of FASN and MAGL to promote nuclear receptor activation and PCa metastasis are critically dependent upon co-expression of FABP5 in vitro and in vivo. Our findings position FABP5 as a key driver of lipid-mediated metastasis and suggest that disruption of lipid signaling via FABP5 inhibition may constitute a new avenue to treat metastatic PCa. Nature Publishing Group UK 2019-12-12 /pmc/articles/PMC6908725/ /pubmed/31831821 http://dx.doi.org/10.1038/s41598-019-55418-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Carbonetti, Gregory Wilpshaar, Tessa Kroonen, Jessie Studholme, Keith Converso, Cynthia d’Oelsnitz, Simon Kaczocha, Martin FABP5 coordinates lipid signaling that promotes prostate cancer metastasis |
title | FABP5 coordinates lipid signaling that promotes prostate cancer metastasis |
title_full | FABP5 coordinates lipid signaling that promotes prostate cancer metastasis |
title_fullStr | FABP5 coordinates lipid signaling that promotes prostate cancer metastasis |
title_full_unstemmed | FABP5 coordinates lipid signaling that promotes prostate cancer metastasis |
title_short | FABP5 coordinates lipid signaling that promotes prostate cancer metastasis |
title_sort | fabp5 coordinates lipid signaling that promotes prostate cancer metastasis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908725/ https://www.ncbi.nlm.nih.gov/pubmed/31831821 http://dx.doi.org/10.1038/s41598-019-55418-x |
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