Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784782238212161536 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9440092 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT kieutrinhlevi downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT pierrelea downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT derangerevalentin downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT perreysabrina downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT truntzercaroline downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT jalilantoine downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT caussesebastien downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT groetzemma downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT dumontadelie downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT guyardlaura downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT arnouldlaurent downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT debarrosjeanpaulpais downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT apetohlionel downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT rebecedric downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT limagneemeric downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT jourdantony downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT demizieuxlaurent downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT massondavid downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT thomascharles downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT ghiringhellifrancois downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors AT riallandmickael downregulationofelovl5promotesbreastcancermetastasisthroughalipiddropletaccumulationmediatedinductionoftgfbreceptors |