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TMEM25 inhibits monomeric EGFR-mediated STAT3 activation in basal state to suppress triple-negative breast cancer progression

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor outcome and lacks of approved targeted therapy. Overexpression of epidermal growth factor receptor (EGFR) is found in more than 50% TNBC and is suggested as a driving force in progression of TNBC; however, targeting EGFR us...

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Autores principales: Bi, Jing, Wu, Zhihui, Zhang, Xin, Zeng, Taoling, Dai, Wanjun, Qiu, Ningyuan, Xu, Mingfeng, Qiao, Yikai, Ke, Lang, Zhao, Jiayi, Cao, Xinyu, Lin, Qi, Chen, Xiao Lei, Xie, Liping, Ouyang, Zhong, Guo, Jujiang, Zheng, Liangkai, Ma, Chao, Guo, Shiying, Chen, Kangmei, Mo, Wei, Fu, Guo, Zhao, Tong-Jin, Wang, Hong-Rui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10126118/
https://www.ncbi.nlm.nih.gov/pubmed/37095176
http://dx.doi.org/10.1038/s41467-023-38115-2
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author Bi, Jing
Wu, Zhihui
Zhang, Xin
Zeng, Taoling
Dai, Wanjun
Qiu, Ningyuan
Xu, Mingfeng
Qiao, Yikai
Ke, Lang
Zhao, Jiayi
Cao, Xinyu
Lin, Qi
Chen, Xiao Lei
Xie, Liping
Ouyang, Zhong
Guo, Jujiang
Zheng, Liangkai
Ma, Chao
Guo, Shiying
Chen, Kangmei
Mo, Wei
Fu, Guo
Zhao, Tong-Jin
Wang, Hong-Rui
author_facet Bi, Jing
Wu, Zhihui
Zhang, Xin
Zeng, Taoling
Dai, Wanjun
Qiu, Ningyuan
Xu, Mingfeng
Qiao, Yikai
Ke, Lang
Zhao, Jiayi
Cao, Xinyu
Lin, Qi
Chen, Xiao Lei
Xie, Liping
Ouyang, Zhong
Guo, Jujiang
Zheng, Liangkai
Ma, Chao
Guo, Shiying
Chen, Kangmei
Mo, Wei
Fu, Guo
Zhao, Tong-Jin
Wang, Hong-Rui
author_sort Bi, Jing
collection PubMed
description Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor outcome and lacks of approved targeted therapy. Overexpression of epidermal growth factor receptor (EGFR) is found in more than 50% TNBC and is suggested as a driving force in progression of TNBC; however, targeting EGFR using antibodies to prevent its dimerization and activation shows no significant benefits for TNBC patients. Here we report that EGFR monomer may activate signal transducer activator of transcription-3 (STAT3) in the absence of transmembrane protein TMEM25, whose expression is frequently decreased in human TNBC. Deficiency of TMEM25 allows EGFR monomer to phosphorylate STAT3 independent of ligand binding, and thus enhances basal STAT3 activation to promote TNBC progression in female mice. Moreover, supplying TMEM25 by adeno-associated virus strongly suppresses STAT3 activation and TNBC progression. Hence, our study reveals a role of monomeric-EGFR/STAT3 signaling pathway in TNBC progression and points out a potential targeted therapy for TNBC.
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spelling pubmed-101261182023-04-26 TMEM25 inhibits monomeric EGFR-mediated STAT3 activation in basal state to suppress triple-negative breast cancer progression Bi, Jing Wu, Zhihui Zhang, Xin Zeng, Taoling Dai, Wanjun Qiu, Ningyuan Xu, Mingfeng Qiao, Yikai Ke, Lang Zhao, Jiayi Cao, Xinyu Lin, Qi Chen, Xiao Lei Xie, Liping Ouyang, Zhong Guo, Jujiang Zheng, Liangkai Ma, Chao Guo, Shiying Chen, Kangmei Mo, Wei Fu, Guo Zhao, Tong-Jin Wang, Hong-Rui Nat Commun Article Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor outcome and lacks of approved targeted therapy. Overexpression of epidermal growth factor receptor (EGFR) is found in more than 50% TNBC and is suggested as a driving force in progression of TNBC; however, targeting EGFR using antibodies to prevent its dimerization and activation shows no significant benefits for TNBC patients. Here we report that EGFR monomer may activate signal transducer activator of transcription-3 (STAT3) in the absence of transmembrane protein TMEM25, whose expression is frequently decreased in human TNBC. Deficiency of TMEM25 allows EGFR monomer to phosphorylate STAT3 independent of ligand binding, and thus enhances basal STAT3 activation to promote TNBC progression in female mice. Moreover, supplying TMEM25 by adeno-associated virus strongly suppresses STAT3 activation and TNBC progression. Hence, our study reveals a role of monomeric-EGFR/STAT3 signaling pathway in TNBC progression and points out a potential targeted therapy for TNBC. Nature Publishing Group UK 2023-04-24 /pmc/articles/PMC10126118/ /pubmed/37095176 http://dx.doi.org/10.1038/s41467-023-38115-2 Text en © The Author(s) 2023 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
Bi, Jing
Wu, Zhihui
Zhang, Xin
Zeng, Taoling
Dai, Wanjun
Qiu, Ningyuan
Xu, Mingfeng
Qiao, Yikai
Ke, Lang
Zhao, Jiayi
Cao, Xinyu
Lin, Qi
Chen, Xiao Lei
Xie, Liping
Ouyang, Zhong
Guo, Jujiang
Zheng, Liangkai
Ma, Chao
Guo, Shiying
Chen, Kangmei
Mo, Wei
Fu, Guo
Zhao, Tong-Jin
Wang, Hong-Rui
TMEM25 inhibits monomeric EGFR-mediated STAT3 activation in basal state to suppress triple-negative breast cancer progression
title TMEM25 inhibits monomeric EGFR-mediated STAT3 activation in basal state to suppress triple-negative breast cancer progression
title_full TMEM25 inhibits monomeric EGFR-mediated STAT3 activation in basal state to suppress triple-negative breast cancer progression
title_fullStr TMEM25 inhibits monomeric EGFR-mediated STAT3 activation in basal state to suppress triple-negative breast cancer progression
title_full_unstemmed TMEM25 inhibits monomeric EGFR-mediated STAT3 activation in basal state to suppress triple-negative breast cancer progression
title_short TMEM25 inhibits monomeric EGFR-mediated STAT3 activation in basal state to suppress triple-negative breast cancer progression
title_sort tmem25 inhibits monomeric egfr-mediated stat3 activation in basal state to suppress triple-negative breast cancer progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10126118/
https://www.ncbi.nlm.nih.gov/pubmed/37095176
http://dx.doi.org/10.1038/s41467-023-38115-2
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