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Sci Rep. 2017 Mar 3;7(1):45. doi: 10.1038/s41598-017-00079-x.

ZEB1 Regulates Multiple Oncogenic Components Involved in Uveal Melanoma Progression.

Author information

1
The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China.
2
Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky, USA.
3
Periodontics, Endodontics, and Dental Hygiene, University of Louisville, Louisville, Kentucky, USA.
4
James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
5
The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China. gaoling6287@163.com.
6
Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky, USA. y0liu016@louisville.edu.
7
James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA. y0liu016@louisville.edu.

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.

PMID:
28246385
PMCID:
PMC5428321
DOI:
10.1038/s41598-017-00079-x
[Indexed for MEDLINE]
Free PMC Article

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