ZEB1 regulates glioma stemness through LIF repression
Abstract The identification of a stem cell regulatory gene which is aberrantly expressed in glioma and associated with patient survival would increase the understanding of the role of glioma cancer stem cells (GCSCs) in the virulence of gliomas. Interrogating the genomes of over 4000 brain cancers w...
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Nature Portfolio
2017
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oai:doaj.org-article:20170381f56644fd9638ce225777a1a92021-12-02T15:05:36ZZEB1 regulates glioma stemness through LIF repression10.1038/s41598-017-00106-x2045-2322https://doaj.org/article/20170381f56644fd9638ce225777a1a92017-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00106-xhttps://doaj.org/toc/2045-2322Abstract The identification of a stem cell regulatory gene which is aberrantly expressed in glioma and associated with patient survival would increase the understanding of the role of glioma cancer stem cells (GCSCs) in the virulence of gliomas. Interrogating the genomes of over 4000 brain cancers we identified ZEB1 deletion in ~15% (grade II and III) and 50% of glioblastomas. Meta-analysis of ZEB1 copy number status in 2,988 cases of glioma revealed disruptive ZEB1 deletions associated with decreased survival. We identified ZEB1 binding sites within the LIF (stemness factor) promoter region, and demonstrate LIF repression by ZEB1. ZEB1 knockdown in GCSCs caused LIF induction commensurate with GCSC self-renewal and inhibition of differentiation. IFN-γ treatment to GCSCs induced ZEB1 expression, attenuating LIF activities. These findings implicate ZEB1 as a stem cell regulator in glioma which when deleted leads to increased stemness, tumorigenicity and shortened patient survival.Lincoln A. EdwardsAiguo LiDror BerelMecca MadanyNam-Ho KimMinzhi LiuMitch HymowitzBenjamin UyRachel JungMinlin XuKeith L. BlackAltan RentsendorjXuemo FanWei ZhangJohn S. YuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
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Medicine R Science Q Lincoln A. Edwards Aiguo Li Dror Berel Mecca Madany Nam-Ho Kim Minzhi Liu Mitch Hymowitz Benjamin Uy Rachel Jung Minlin Xu Keith L. Black Altan Rentsendorj Xuemo Fan Wei Zhang John S. Yu ZEB1 regulates glioma stemness through LIF repression |
| description |
Abstract The identification of a stem cell regulatory gene which is aberrantly expressed in glioma and associated with patient survival would increase the understanding of the role of glioma cancer stem cells (GCSCs) in the virulence of gliomas. Interrogating the genomes of over 4000 brain cancers we identified ZEB1 deletion in ~15% (grade II and III) and 50% of glioblastomas. Meta-analysis of ZEB1 copy number status in 2,988 cases of glioma revealed disruptive ZEB1 deletions associated with decreased survival. We identified ZEB1 binding sites within the LIF (stemness factor) promoter region, and demonstrate LIF repression by ZEB1. ZEB1 knockdown in GCSCs caused LIF induction commensurate with GCSC self-renewal and inhibition of differentiation. IFN-γ treatment to GCSCs induced ZEB1 expression, attenuating LIF activities. These findings implicate ZEB1 as a stem cell regulator in glioma which when deleted leads to increased stemness, tumorigenicity and shortened patient survival. |
| format |
article |
| author |
Lincoln A. Edwards Aiguo Li Dror Berel Mecca Madany Nam-Ho Kim Minzhi Liu Mitch Hymowitz Benjamin Uy Rachel Jung Minlin Xu Keith L. Black Altan Rentsendorj Xuemo Fan Wei Zhang John S. Yu |
| author_facet |
Lincoln A. Edwards Aiguo Li Dror Berel Mecca Madany Nam-Ho Kim Minzhi Liu Mitch Hymowitz Benjamin Uy Rachel Jung Minlin Xu Keith L. Black Altan Rentsendorj Xuemo Fan Wei Zhang John S. Yu |
| author_sort |
Lincoln A. Edwards |
| title |
ZEB1 regulates glioma stemness through LIF repression |
| title_short |
ZEB1 regulates glioma stemness through LIF repression |
| title_full |
ZEB1 regulates glioma stemness through LIF repression |
| title_fullStr |
ZEB1 regulates glioma stemness through LIF repression |
| title_full_unstemmed |
ZEB1 regulates glioma stemness through LIF repression |
| title_sort |
zeb1 regulates glioma stemness through lif repression |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/20170381f56644fd9638ce225777a1a9 |
| work_keys_str_mv |
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