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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...

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Autores principales: Carbonetti, Gregory, Wilpshaar, Tessa, Kroonen, Jessie, Studholme, Keith, Converso, Cynthia, d’Oelsnitz, Simon, Kaczocha, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
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.
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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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