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Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis
Loss of WW domain-containing oxidoreductase (Wwox) expression has been observed in breast cancer (BC). However, its regulatory effects are largely unknown, especially in triple-negative breast cancer (TNBC). Herein, gene expression profiling revealed that JAK/STAT3 pathway was one of the most differ...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113304/ https://www.ncbi.nlm.nih.gov/pubmed/30154439 http://dx.doi.org/10.1038/s41467-018-05852-8 |
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author | Chang, Renxu Song, Lele Xu, Yi Wu, Yanjun Dai, Cheng Wang, Xinyu Sun, Xia Hou, Yingyong Li, Wei Zhan, Xianbao Zhan, Lixing |
author_facet | Chang, Renxu Song, Lele Xu, Yi Wu, Yanjun Dai, Cheng Wang, Xinyu Sun, Xia Hou, Yingyong Li, Wei Zhan, Xianbao Zhan, Lixing |
author_sort | Chang, Renxu |
collection | PubMed |
description | Loss of WW domain-containing oxidoreductase (Wwox) expression has been observed in breast cancer (BC). However, its regulatory effects are largely unknown, especially in triple-negative breast cancer (TNBC). Herein, gene expression profiling revealed that JAK/STAT3 pathway was one of the most differentially modulated pathways in basal-like BC cells. The lower expression of Wwox was significantly correlated with high activation of STAT3 in basal-like cells and TNBC tissues. Overexpression of Wwox markedly inhibited proliferation and metastasis of BC cells by suppressing STAT3 activation, which is to interact with JAK2 to inhibit JAK2 and STAT3 phosphorylation. Furthermore, Wwox limited STAT3 binding to the interleukin-6 promoter, repressing expression of the IL-6 cytokine. Altogether, our data established that Wwox suppresses BC cell metastasis and proliferation by JAK2/STAT3 pathway. Targeting of Wwox with STAT3 could offer a promising therapeutic strategy for TNBC. |
format | Online Article Text |
id | pubmed-6113304 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61133042018-08-30 Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis Chang, Renxu Song, Lele Xu, Yi Wu, Yanjun Dai, Cheng Wang, Xinyu Sun, Xia Hou, Yingyong Li, Wei Zhan, Xianbao Zhan, Lixing Nat Commun Article Loss of WW domain-containing oxidoreductase (Wwox) expression has been observed in breast cancer (BC). However, its regulatory effects are largely unknown, especially in triple-negative breast cancer (TNBC). Herein, gene expression profiling revealed that JAK/STAT3 pathway was one of the most differentially modulated pathways in basal-like BC cells. The lower expression of Wwox was significantly correlated with high activation of STAT3 in basal-like cells and TNBC tissues. Overexpression of Wwox markedly inhibited proliferation and metastasis of BC cells by suppressing STAT3 activation, which is to interact with JAK2 to inhibit JAK2 and STAT3 phosphorylation. Furthermore, Wwox limited STAT3 binding to the interleukin-6 promoter, repressing expression of the IL-6 cytokine. Altogether, our data established that Wwox suppresses BC cell metastasis and proliferation by JAK2/STAT3 pathway. Targeting of Wwox with STAT3 could offer a promising therapeutic strategy for TNBC. Nature Publishing Group UK 2018-08-28 /pmc/articles/PMC6113304/ /pubmed/30154439 http://dx.doi.org/10.1038/s41467-018-05852-8 Text en © The Author(s) 2018 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/. |
spellingShingle | Article Chang, Renxu Song, Lele Xu, Yi Wu, Yanjun Dai, Cheng Wang, Xinyu Sun, Xia Hou, Yingyong Li, Wei Zhan, Xianbao Zhan, Lixing Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis |
title | Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis |
title_full | Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis |
title_fullStr | Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis |
title_full_unstemmed | Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis |
title_short | Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis |
title_sort | loss of wwox drives metastasis in triple-negative breast cancer by jak2/stat3 axis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113304/ https://www.ncbi.nlm.nih.gov/pubmed/30154439 http://dx.doi.org/10.1038/s41467-018-05852-8 |
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