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Downregulation of Elovl5 promotes breast cancer metastasis through a lipid-droplet accumulation-mediated induction of TGF-β receptors

Metastatic breast cancer cannot be cured, and alteration of fatty acid metabolism contributes to tumor progression and metastasis. Here, we were interested in the elongation of very long-chain fatty acids protein 5 (Elovl5) in breast cancer. We observed that breast cancer tumors had a lower expressi...

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Autores principales: Kieu, Trinh-Le-Vi, Pierre, Léa, Derangère, Valentin, Perrey, Sabrina, Truntzer, Caroline, Jalil, Antoine, Causse, Sébastien, Groetz, Emma, Dumont, Adélie, Guyard, Laura, Arnould, Laurent, de Barros, Jean-Paul Pais, Apetoh, Lionel, Rébé, Cédric, Limagne, Emeric, Jourdan, Tony, Demizieux, Laurent, Masson, David, Thomas, Charles, Ghiringhelli, François, Rialland, Mickaël
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9440092/
https://www.ncbi.nlm.nih.gov/pubmed/36056008
http://dx.doi.org/10.1038/s41419-022-05209-6
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author Kieu, Trinh-Le-Vi
Pierre, Léa
Derangère, Valentin
Perrey, Sabrina
Truntzer, Caroline
Jalil, Antoine
Causse, Sébastien
Groetz, Emma
Dumont, Adélie
Guyard, Laura
Arnould, Laurent
de Barros, Jean-Paul Pais
Apetoh, Lionel
Rébé, Cédric
Limagne, Emeric
Jourdan, Tony
Demizieux, Laurent
Masson, David
Thomas, Charles
Ghiringhelli, François
Rialland, Mickaël
author_facet Kieu, Trinh-Le-Vi
Pierre, Léa
Derangère, Valentin
Perrey, Sabrina
Truntzer, Caroline
Jalil, Antoine
Causse, Sébastien
Groetz, Emma
Dumont, Adélie
Guyard, Laura
Arnould, Laurent
de Barros, Jean-Paul Pais
Apetoh, Lionel
Rébé, Cédric
Limagne, Emeric
Jourdan, Tony
Demizieux, Laurent
Masson, David
Thomas, Charles
Ghiringhelli, François
Rialland, Mickaël
author_sort Kieu, Trinh-Le-Vi
collection PubMed
description Metastatic breast cancer cannot be cured, and alteration of fatty acid metabolism contributes to tumor progression and metastasis. Here, we were interested in the elongation of very long-chain fatty acids protein 5 (Elovl5) in breast cancer. We observed that breast cancer tumors had a lower expression of Elovl5 than normal breast tissues. Furthermore, low expression of Elovl5 is associated with a worse prognosis in ER(+) breast cancer patients. In accordance with this finding, decrease of Elovl5 expression was more pronounced in ER(+) breast tumors from patients with metastases in lymph nodes. Although downregulation of Elovl5 expression limited breast cancer cell proliferation and cancer progression, suppression of Elovl5 promoted EMT, cell invasion and lung metastases in murine breast cancer models. The loss of Elovl5 expression induced upregulation of TGF-β receptors mediated by a lipid-droplet accumulation-dependent Smad2 acetylation. As expected, inhibition of TGF-β receptors restored proliferation and dampened invasion in low Elovl5 expressing cancer cells. Interestingly, the abolition of lipid-droplet formation by inhibition of diacylglycerol acyltransferase activity reversed induction of TGF-β receptors, cell invasion, and lung metastasis triggered by Elovl5 knockdown. Altogether, we showed that Elovl5 is involved in metastasis through lipid droplets-regulated TGF-β receptor expression and is a predictive biomarker of metastatic ER(+) breast cancer.
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spelling pubmed-94400922022-09-04 Downregulation of Elovl5 promotes breast cancer metastasis through a lipid-droplet accumulation-mediated induction of TGF-β receptors Kieu, Trinh-Le-Vi Pierre, Léa Derangère, Valentin Perrey, Sabrina Truntzer, Caroline Jalil, Antoine Causse, Sébastien Groetz, Emma Dumont, Adélie Guyard, Laura Arnould, Laurent de Barros, Jean-Paul Pais Apetoh, Lionel Rébé, Cédric Limagne, Emeric Jourdan, Tony Demizieux, Laurent Masson, David Thomas, Charles Ghiringhelli, François Rialland, Mickaël Cell Death Dis Article Metastatic breast cancer cannot be cured, and alteration of fatty acid metabolism contributes to tumor progression and metastasis. Here, we were interested in the elongation of very long-chain fatty acids protein 5 (Elovl5) in breast cancer. We observed that breast cancer tumors had a lower expression of Elovl5 than normal breast tissues. Furthermore, low expression of Elovl5 is associated with a worse prognosis in ER(+) breast cancer patients. In accordance with this finding, decrease of Elovl5 expression was more pronounced in ER(+) breast tumors from patients with metastases in lymph nodes. Although downregulation of Elovl5 expression limited breast cancer cell proliferation and cancer progression, suppression of Elovl5 promoted EMT, cell invasion and lung metastases in murine breast cancer models. The loss of Elovl5 expression induced upregulation of TGF-β receptors mediated by a lipid-droplet accumulation-dependent Smad2 acetylation. As expected, inhibition of TGF-β receptors restored proliferation and dampened invasion in low Elovl5 expressing cancer cells. Interestingly, the abolition of lipid-droplet formation by inhibition of diacylglycerol acyltransferase activity reversed induction of TGF-β receptors, cell invasion, and lung metastasis triggered by Elovl5 knockdown. Altogether, we showed that Elovl5 is involved in metastasis through lipid droplets-regulated TGF-β receptor expression and is a predictive biomarker of metastatic ER(+) breast cancer. Nature Publishing Group UK 2022-09-02 /pmc/articles/PMC9440092/ /pubmed/36056008 http://dx.doi.org/10.1038/s41419-022-05209-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kieu, Trinh-Le-Vi
Pierre, Léa
Derangère, Valentin
Perrey, Sabrina
Truntzer, Caroline
Jalil, Antoine
Causse, Sébastien
Groetz, Emma
Dumont, Adélie
Guyard, Laura
Arnould, Laurent
de Barros, Jean-Paul Pais
Apetoh, Lionel
Rébé, Cédric
Limagne, Emeric
Jourdan, Tony
Demizieux, Laurent
Masson, David
Thomas, Charles
Ghiringhelli, François
Rialland, Mickaël
Downregulation of Elovl5 promotes breast cancer metastasis through a lipid-droplet accumulation-mediated induction of TGF-β receptors
title Downregulation of Elovl5 promotes breast cancer metastasis through a lipid-droplet accumulation-mediated induction of TGF-β receptors
title_full Downregulation of Elovl5 promotes breast cancer metastasis through a lipid-droplet accumulation-mediated induction of TGF-β receptors
title_fullStr Downregulation of Elovl5 promotes breast cancer metastasis through a lipid-droplet accumulation-mediated induction of TGF-β receptors
title_full_unstemmed Downregulation of Elovl5 promotes breast cancer metastasis through a lipid-droplet accumulation-mediated induction of TGF-β receptors
title_short Downregulation of Elovl5 promotes breast cancer metastasis through a lipid-droplet accumulation-mediated induction of TGF-β receptors
title_sort downregulation of elovl5 promotes breast cancer metastasis through a lipid-droplet accumulation-mediated induction of tgf-β receptors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9440092/
https://www.ncbi.nlm.nih.gov/pubmed/36056008
http://dx.doi.org/10.1038/s41419-022-05209-6
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