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Enhanced CHOLESTEROL biosynthesis promotes breast cancer metastasis via modulating CCDC25 expression and neutrophil extracellular traps formation
Neutrophil extracellular traps (NETs) has been demonstrated to regulate the metastasis of breast cancer. In this study, we showed that de novo cholesterol biosynthesis induced by ASPP2 depletion in mouse breast cancer cell 4T1 and human breast cancer cell MDA-MB-231 promoted NETs formation in vitro,...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576744/ https://www.ncbi.nlm.nih.gov/pubmed/36253427 http://dx.doi.org/10.1038/s41598-022-22410-x |
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author | Tang, Qiqi Liang, Beibei Zhang, Lisha Li, Xuhui Li, Hengyu Jing, Wei Jiang, Yingjie Zhou, Felix Zhang, Jian Meng, Yanchun Yang, Xinhua Yang, Hao Huang, Gang Zhao, Jian |
author_facet | Tang, Qiqi Liang, Beibei Zhang, Lisha Li, Xuhui Li, Hengyu Jing, Wei Jiang, Yingjie Zhou, Felix Zhang, Jian Meng, Yanchun Yang, Xinhua Yang, Hao Huang, Gang Zhao, Jian |
author_sort | Tang, Qiqi |
collection | PubMed |
description | Neutrophil extracellular traps (NETs) has been demonstrated to regulate the metastasis of breast cancer. In this study, we showed that de novo cholesterol biosynthesis induced by ASPP2 depletion in mouse breast cancer cell 4T1 and human breast cancer cell MDA-MB-231 promoted NETs formation in vitro, as well as in lung metastases in mice intravenously injected with ASPP2-deficient 4T1 cells. Simvastatin and berberine (BBR), cholesterol synthesis inhibitors, efficiently blocked ASPP2-depletion induced NETs formation. Cholesterol biosynthesis greatly enhanced Coiled-coil domain containing protein 25 (CCDC25) expression on cancer cells as well as in lung metastases. CCDC25 expression was co-localized with caveolin-1, a lipid raft molecule, and was damped by inhibitor of lipid rafts formation. Our data suggest that cholesterol biosynthesis promotes CCDC25 expression in a lipid raft-dependent manner. Clinically, the expression of CCDC25 was positively correlated with the expression of 3-hydroxy-3-methylglutaryl-CoAreductase (HMRCG), and citrullinated histone H3 (H3cit), in tissues from breast cancer patients. High expression of CCDC25 and HMGCR was related with worse prognosis in breast cancer patients. In conclusion, our study explores a novel mechanism for de novo cholesterol biosynthesis in the regulation of CCDC25 expression, NETs formation and breast cancer metastasis. Targeting cholesterol biosynthesis may be promising therapeutic strategies to treat breast cancer metastasis. |
format | Online Article Text |
id | pubmed-9576744 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-95767442022-10-19 Enhanced CHOLESTEROL biosynthesis promotes breast cancer metastasis via modulating CCDC25 expression and neutrophil extracellular traps formation Tang, Qiqi Liang, Beibei Zhang, Lisha Li, Xuhui Li, Hengyu Jing, Wei Jiang, Yingjie Zhou, Felix Zhang, Jian Meng, Yanchun Yang, Xinhua Yang, Hao Huang, Gang Zhao, Jian Sci Rep Article Neutrophil extracellular traps (NETs) has been demonstrated to regulate the metastasis of breast cancer. In this study, we showed that de novo cholesterol biosynthesis induced by ASPP2 depletion in mouse breast cancer cell 4T1 and human breast cancer cell MDA-MB-231 promoted NETs formation in vitro, as well as in lung metastases in mice intravenously injected with ASPP2-deficient 4T1 cells. Simvastatin and berberine (BBR), cholesterol synthesis inhibitors, efficiently blocked ASPP2-depletion induced NETs formation. Cholesterol biosynthesis greatly enhanced Coiled-coil domain containing protein 25 (CCDC25) expression on cancer cells as well as in lung metastases. CCDC25 expression was co-localized with caveolin-1, a lipid raft molecule, and was damped by inhibitor of lipid rafts formation. Our data suggest that cholesterol biosynthesis promotes CCDC25 expression in a lipid raft-dependent manner. Clinically, the expression of CCDC25 was positively correlated with the expression of 3-hydroxy-3-methylglutaryl-CoAreductase (HMRCG), and citrullinated histone H3 (H3cit), in tissues from breast cancer patients. High expression of CCDC25 and HMGCR was related with worse prognosis in breast cancer patients. In conclusion, our study explores a novel mechanism for de novo cholesterol biosynthesis in the regulation of CCDC25 expression, NETs formation and breast cancer metastasis. Targeting cholesterol biosynthesis may be promising therapeutic strategies to treat breast cancer metastasis. Nature Publishing Group UK 2022-10-17 /pmc/articles/PMC9576744/ /pubmed/36253427 http://dx.doi.org/10.1038/s41598-022-22410-x 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Tang, Qiqi Liang, Beibei Zhang, Lisha Li, Xuhui Li, Hengyu Jing, Wei Jiang, Yingjie Zhou, Felix Zhang, Jian Meng, Yanchun Yang, Xinhua Yang, Hao Huang, Gang Zhao, Jian Enhanced CHOLESTEROL biosynthesis promotes breast cancer metastasis via modulating CCDC25 expression and neutrophil extracellular traps formation |
title | Enhanced CHOLESTEROL biosynthesis promotes breast cancer metastasis via modulating CCDC25 expression and neutrophil extracellular traps formation |
title_full | Enhanced CHOLESTEROL biosynthesis promotes breast cancer metastasis via modulating CCDC25 expression and neutrophil extracellular traps formation |
title_fullStr | Enhanced CHOLESTEROL biosynthesis promotes breast cancer metastasis via modulating CCDC25 expression and neutrophil extracellular traps formation |
title_full_unstemmed | Enhanced CHOLESTEROL biosynthesis promotes breast cancer metastasis via modulating CCDC25 expression and neutrophil extracellular traps formation |
title_short | Enhanced CHOLESTEROL biosynthesis promotes breast cancer metastasis via modulating CCDC25 expression and neutrophil extracellular traps formation |
title_sort | enhanced cholesterol biosynthesis promotes breast cancer metastasis via modulating ccdc25 expression and neutrophil extracellular traps formation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576744/ https://www.ncbi.nlm.nih.gov/pubmed/36253427 http://dx.doi.org/10.1038/s41598-022-22410-x |
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