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ZEB1 confers stem cell-like properties in breast cancer by targeting neurogenin-3

Cancer stem cells (CSCs) are a subpopulation of cancer cells believed to be implicated in cancer initiation, progression, and recurrence. Here, we report that ectopic expression of zinc finger E-box binding homeobox 1 protein (ZEB1) results in the acquisition of CSC properties by breast cancer cells...

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Autores principales: Zhou, Chen, Jiang, Huimin, Zhang, Zhen, Zhang, Guomin, Wang, Hang, Zhang, Quansheng, Sun, Peiqing, Xiang, Rong, Yang, Shuang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589589/
https://www.ncbi.nlm.nih.gov/pubmed/28903350
http://dx.doi.org/10.18632/oncotarget.17077
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author Zhou, Chen
Jiang, Huimin
Zhang, Zhen
Zhang, Guomin
Wang, Hang
Zhang, Quansheng
Sun, Peiqing
Xiang, Rong
Yang, Shuang
author_facet Zhou, Chen
Jiang, Huimin
Zhang, Zhen
Zhang, Guomin
Wang, Hang
Zhang, Quansheng
Sun, Peiqing
Xiang, Rong
Yang, Shuang
author_sort Zhou, Chen
collection PubMed
description Cancer stem cells (CSCs) are a subpopulation of cancer cells believed to be implicated in cancer initiation, progression, and recurrence. Here, we report that ectopic expression of zinc finger E-box binding homeobox 1 protein (ZEB1) results in the acquisition of CSC properties by breast cancer cells, leading to tumor initiation and progression in vitro and in vivo. The neurogenin 3 gene (Ngn3) is a bona fide target of ZEB1, and its repression is a key factor contributing to ZEB1-induced cancer cell stemness. ZEB1 suppressed Ngn3 transcription by forming a ZEB1/DNA methyltransferase (DNMT)3B/histone deacetylase 1 (HDAC1) complex on the Ngn3 promoter, leading to promoter hypermethylation and gene silencing. The rescue of Ngn3 expression attenuated ZEB1-induced cancer stemness and symmetric CSC division. Immunohistological analysis of human breast cancer specimens revealed a strong inverse relationship between ZEB1 and NGN3 protein expression. Thus, our findings suggest ZEB1-mediated silencing of Ngn3 is required for breast tumor initiation and maintenance. Targeted therapies against the ZEB1/Ngn3 axis may be highly valuable for the prevention and treatment of breast cancer.
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spelling pubmed-55895892017-09-12 ZEB1 confers stem cell-like properties in breast cancer by targeting neurogenin-3 Zhou, Chen Jiang, Huimin Zhang, Zhen Zhang, Guomin Wang, Hang Zhang, Quansheng Sun, Peiqing Xiang, Rong Yang, Shuang Oncotarget Research Paper Cancer stem cells (CSCs) are a subpopulation of cancer cells believed to be implicated in cancer initiation, progression, and recurrence. Here, we report that ectopic expression of zinc finger E-box binding homeobox 1 protein (ZEB1) results in the acquisition of CSC properties by breast cancer cells, leading to tumor initiation and progression in vitro and in vivo. The neurogenin 3 gene (Ngn3) is a bona fide target of ZEB1, and its repression is a key factor contributing to ZEB1-induced cancer cell stemness. ZEB1 suppressed Ngn3 transcription by forming a ZEB1/DNA methyltransferase (DNMT)3B/histone deacetylase 1 (HDAC1) complex on the Ngn3 promoter, leading to promoter hypermethylation and gene silencing. The rescue of Ngn3 expression attenuated ZEB1-induced cancer stemness and symmetric CSC division. Immunohistological analysis of human breast cancer specimens revealed a strong inverse relationship between ZEB1 and NGN3 protein expression. Thus, our findings suggest ZEB1-mediated silencing of Ngn3 is required for breast tumor initiation and maintenance. Targeted therapies against the ZEB1/Ngn3 axis may be highly valuable for the prevention and treatment of breast cancer. Impact Journals LLC 2017-04-13 /pmc/articles/PMC5589589/ /pubmed/28903350 http://dx.doi.org/10.18632/oncotarget.17077 Text en Copyright: © 2017 Zhou et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zhou, Chen
Jiang, Huimin
Zhang, Zhen
Zhang, Guomin
Wang, Hang
Zhang, Quansheng
Sun, Peiqing
Xiang, Rong
Yang, Shuang
ZEB1 confers stem cell-like properties in breast cancer by targeting neurogenin-3
title ZEB1 confers stem cell-like properties in breast cancer by targeting neurogenin-3
title_full ZEB1 confers stem cell-like properties in breast cancer by targeting neurogenin-3
title_fullStr ZEB1 confers stem cell-like properties in breast cancer by targeting neurogenin-3
title_full_unstemmed ZEB1 confers stem cell-like properties in breast cancer by targeting neurogenin-3
title_short ZEB1 confers stem cell-like properties in breast cancer by targeting neurogenin-3
title_sort zeb1 confers stem cell-like properties in breast cancer by targeting neurogenin-3
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589589/
https://www.ncbi.nlm.nih.gov/pubmed/28903350
http://dx.doi.org/10.18632/oncotarget.17077
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