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Fascin enhances the vulnerability of breast cancer to erastin-induced ferroptosis

Ferroptosis, which is characterized by intracellular iron accumulation and lipid peroxidation, is a newly described form of regulated cell death that may play a key role in tumour suppression. In the present study, we investigated the expression profiles and biological effects of fascin actin-bundli...

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Autores principales: Chen, Cong, Xie, Bojian, Li, Zhaoqing, Chen, Lini, Chen, Yongxia, Zhou, Jichun, Ju, Siwei, Zhou, Yulu, Zhang, Xun, Zhuo, Wenying, Yang, Jingjing, Mao, Misha, Xu, Ling, Wang, Linbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8844358/
https://www.ncbi.nlm.nih.gov/pubmed/35165254
http://dx.doi.org/10.1038/s41419-022-04579-1
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author Chen, Cong
Xie, Bojian
Li, Zhaoqing
Chen, Lini
Chen, Yongxia
Zhou, Jichun
Ju, Siwei
Zhou, Yulu
Zhang, Xun
Zhuo, Wenying
Yang, Jingjing
Mao, Misha
Xu, Ling
Wang, Linbo
author_facet Chen, Cong
Xie, Bojian
Li, Zhaoqing
Chen, Lini
Chen, Yongxia
Zhou, Jichun
Ju, Siwei
Zhou, Yulu
Zhang, Xun
Zhuo, Wenying
Yang, Jingjing
Mao, Misha
Xu, Ling
Wang, Linbo
author_sort Chen, Cong
collection PubMed
description Ferroptosis, which is characterized by intracellular iron accumulation and lipid peroxidation, is a newly described form of regulated cell death that may play a key role in tumour suppression. In the present study, we investigated the expression profiles and biological effects of fascin actin-bundling protein 1 (Fascin, gene name FSCN1) in breast cancer. In addition, bioinformatics analysis of the TCGA cancer database and gain- and loss-of-function studies showed that Fascin enhances sensitivity to erastin-induced ferroptosis. Mechanistically, Fascin directly interacts with cysteine/glutamate transporter (xCT, gene name SLC7A11) and decreases its stability via the ubiquitin-mediated proteasome degradation pathway. Furthermore, we observed that Fascin is substantially upregulated in tamoxifen-resistant breast cancer cell lines, and drug-resistant cells were also more vulnerable to erastin-induced ferroptosis. Taken together, our findings reveal a previously unidentified role of Fascin in ferroptosis by regulating xCT. Thus, ferroptosis activation in breast cancer with high Fascin level may serve as a potential treatment.
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spelling pubmed-88443582022-03-04 Fascin enhances the vulnerability of breast cancer to erastin-induced ferroptosis Chen, Cong Xie, Bojian Li, Zhaoqing Chen, Lini Chen, Yongxia Zhou, Jichun Ju, Siwei Zhou, Yulu Zhang, Xun Zhuo, Wenying Yang, Jingjing Mao, Misha Xu, Ling Wang, Linbo Cell Death Dis Article Ferroptosis, which is characterized by intracellular iron accumulation and lipid peroxidation, is a newly described form of regulated cell death that may play a key role in tumour suppression. In the present study, we investigated the expression profiles and biological effects of fascin actin-bundling protein 1 (Fascin, gene name FSCN1) in breast cancer. In addition, bioinformatics analysis of the TCGA cancer database and gain- and loss-of-function studies showed that Fascin enhances sensitivity to erastin-induced ferroptosis. Mechanistically, Fascin directly interacts with cysteine/glutamate transporter (xCT, gene name SLC7A11) and decreases its stability via the ubiquitin-mediated proteasome degradation pathway. Furthermore, we observed that Fascin is substantially upregulated in tamoxifen-resistant breast cancer cell lines, and drug-resistant cells were also more vulnerable to erastin-induced ferroptosis. Taken together, our findings reveal a previously unidentified role of Fascin in ferroptosis by regulating xCT. Thus, ferroptosis activation in breast cancer with high Fascin level may serve as a potential treatment. Nature Publishing Group UK 2022-02-14 /pmc/articles/PMC8844358/ /pubmed/35165254 http://dx.doi.org/10.1038/s41419-022-04579-1 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
Chen, Cong
Xie, Bojian
Li, Zhaoqing
Chen, Lini
Chen, Yongxia
Zhou, Jichun
Ju, Siwei
Zhou, Yulu
Zhang, Xun
Zhuo, Wenying
Yang, Jingjing
Mao, Misha
Xu, Ling
Wang, Linbo
Fascin enhances the vulnerability of breast cancer to erastin-induced ferroptosis
title Fascin enhances the vulnerability of breast cancer to erastin-induced ferroptosis
title_full Fascin enhances the vulnerability of breast cancer to erastin-induced ferroptosis
title_fullStr Fascin enhances the vulnerability of breast cancer to erastin-induced ferroptosis
title_full_unstemmed Fascin enhances the vulnerability of breast cancer to erastin-induced ferroptosis
title_short Fascin enhances the vulnerability of breast cancer to erastin-induced ferroptosis
title_sort fascin enhances the vulnerability of breast cancer to erastin-induced ferroptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8844358/
https://www.ncbi.nlm.nih.gov/pubmed/35165254
http://dx.doi.org/10.1038/s41419-022-04579-1
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