Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783262360826281984 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5589589 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT zhouchen zeb1confersstemcelllikepropertiesinbreastcancerbytargetingneurogenin3 AT jianghuimin zeb1confersstemcelllikepropertiesinbreastcancerbytargetingneurogenin3 AT zhangzhen zeb1confersstemcelllikepropertiesinbreastcancerbytargetingneurogenin3 AT zhangguomin zeb1confersstemcelllikepropertiesinbreastcancerbytargetingneurogenin3 AT wanghang zeb1confersstemcelllikepropertiesinbreastcancerbytargetingneurogenin3 AT zhangquansheng zeb1confersstemcelllikepropertiesinbreastcancerbytargetingneurogenin3 AT sunpeiqing zeb1confersstemcelllikepropertiesinbreastcancerbytargetingneurogenin3 AT xiangrong zeb1confersstemcelllikepropertiesinbreastcancerbytargetingneurogenin3 AT yangshuang zeb1confersstemcelllikepropertiesinbreastcancerbytargetingneurogenin3 |