title: 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 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.
authors.affiliation: The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China.|Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Diego E
authors.initials: DE
authors.lastname: Montoya-Durango
authors.affiliation: The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Dean
authors.affiliation: Periodontics, Endodontics, and Dental Hygiene, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Darling
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Kaplan
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky, USA.|James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Dean
authors.affiliation: The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China. gaoling6287@163.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky, USA. y0liu016@louisville.edu.|James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA. y0liu016@louisville.edu.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D054337:Cell Dedifferentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009857:Oncogenes; D014604:Uveal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000235:genetics* / Q000378:metabolism; D000098943:Uveal Melanoma
chemical_list: C486307:ZEB1 protein, human; C519422:ZEB1 protein, mouse; D000071799:Zinc Finger E-box-Binding Homeobox 1