ZEB1 Regulates Multiple Oncogenic Components Involved in Uveal Melanoma Progression

Abstract Human uveal melanoma (UM) is a major ocular malignant tumor with high risk of metastasis and requires multiple oncogenic factors for progression. ZEB1 is a zinc finger E-box binding transcription factor known for participating epithelial-mesenchymal transition (EMT), a critical cellular eve...

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Autores principales:	Yao Chen, Xiaoqin Lu, Diego E. Montoya-Durango, Yu-Hua Liu, Kevin C. Dean, Douglas S. Darling, Henry J. Kaplan, Douglas C. Dean, Ling Gao, Yongqing Liu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/384daa64ce3f4036858f348b898b32c6
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spelling	oai:doaj.org-article:384daa64ce3f4036858f348b898b32c62021-12-02T16:06:44ZZEB1 Regulates Multiple Oncogenic Components Involved in Uveal Melanoma Progression10.1038/s41598-017-00079-x2045-2322https://doaj.org/article/384daa64ce3f4036858f348b898b32c62017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00079-xhttps://doaj.org/toc/2045-2322Abstract Human uveal melanoma (UM) is a major ocular malignant tumor with high risk of metastasis and requires multiple oncogenic factors for progression. ZEB1 is a zinc finger E-box binding transcription factor known for participating epithelial-mesenchymal transition (EMT), a critical cellular event for metastasis of malignant tumors of epithelium origin. ZEB1 is also expressed in UM and high expression of ZEB1 correlates with UM advancement, but has little effect on cell morphology. We show that spindle UM cells can become epithelioid but not vice versa; and ZEB1 exerts its tumorigenic effects by promoting cell dedifferentiation, proliferation, invasiveness, and dissemination. We provide evidence that ZEB1 binds not only to repress critical genes involving in pigment synthesis, mitosis, adherent junctions, but also to transactivate genes involving in matrix degradation and cellular locomotion to propel UM progression towards metastasis. We conclude that ZEB1 is a major oncogenic factor required for UM progression and could be a potential therapeutic target for treating UM in the clinic.Yao ChenXiaoqin LuDiego E. Montoya-DurangoYu-Hua LiuKevin C. DeanDouglas S. DarlingHenry J. KaplanDouglas C. DeanLing GaoYongqing LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yao Chen Xiaoqin Lu Diego E. Montoya-Durango Yu-Hua Liu Kevin C. Dean Douglas S. Darling Henry J. Kaplan Douglas C. Dean Ling Gao Yongqing Liu ZEB1 Regulates Multiple Oncogenic Components Involved in Uveal Melanoma Progression
description	Abstract Human uveal melanoma (UM) is a major ocular malignant tumor with high risk of metastasis and requires multiple oncogenic factors for progression. ZEB1 is a zinc finger E-box binding transcription factor known for participating epithelial-mesenchymal transition (EMT), a critical cellular event for metastasis of malignant tumors of epithelium origin. ZEB1 is also expressed in UM and high expression of ZEB1 correlates with UM advancement, but has little effect on cell morphology. We show that spindle UM cells can become epithelioid but not vice versa; and ZEB1 exerts its tumorigenic effects by promoting cell dedifferentiation, proliferation, invasiveness, and dissemination. We provide evidence that ZEB1 binds not only to repress critical genes involving in pigment synthesis, mitosis, adherent junctions, but also to transactivate genes involving in matrix degradation and cellular locomotion to propel UM progression towards metastasis. We conclude that ZEB1 is a major oncogenic factor required for UM progression and could be a potential therapeutic target for treating UM in the clinic.
format	article
author	Yao Chen Xiaoqin Lu Diego E. Montoya-Durango Yu-Hua Liu Kevin C. Dean Douglas S. Darling Henry J. Kaplan Douglas C. Dean Ling Gao Yongqing Liu
author_facet	Yao Chen Xiaoqin Lu Diego E. Montoya-Durango Yu-Hua Liu Kevin C. Dean Douglas S. Darling Henry J. Kaplan Douglas C. Dean Ling Gao Yongqing Liu
author_sort	Yao Chen
title	ZEB1 Regulates Multiple Oncogenic Components Involved in Uveal Melanoma Progression
title_short	ZEB1 Regulates Multiple Oncogenic Components Involved in Uveal Melanoma Progression
title_full	ZEB1 Regulates Multiple Oncogenic Components Involved in Uveal Melanoma Progression
title_fullStr	ZEB1 Regulates Multiple Oncogenic Components Involved in Uveal Melanoma Progression
title_full_unstemmed	ZEB1 Regulates Multiple Oncogenic Components Involved in Uveal Melanoma Progression
title_sort	zeb1 regulates multiple oncogenic components involved in uveal melanoma progression
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/384daa64ce3f4036858f348b898b32c6
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ZEB1 Regulates Multiple Oncogenic Components Involved in Uveal Melanoma Progression

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