title: Decrease of ZEB1 expression inhibits the B16F10 cancer stem-like properties.
abstract: Increasing evidence supports that cancer stem cells (CSCs) are responsible for driving tumor initiation and maintenance. Zinc-finger E-box binding homeobox 1 (ZEB1) is a transcription factor for regulating tumor progression, and contributes to maintenance of CSC-like properties. The goal of the present study is to investigate the effect of decreasing ZEB1 expression on the B16F10 CSC-like properties. The recombinant shRNA targeting ZEB1 were transfected into melanoma B16F10 cells, and shZEB1-CD133(+)CD44(+) CSCs were isolated from the stable transfected cells using the magnetic-associated cell sorting method. The shZEB1-CD133(+)CD44(+) CSC-like properties were systematically analyzed. The results show the B16F10 shZEB1-CD133(+)CD44(+) CSCs significantly decreased the ability of clonogenicity, cellular proliferation, migration, and invasion. Importantly, tumorigenicity and tumor lung metastasis was significantly inhibited in B16F10 shZEB1-CD133(+)CD44(+) CSCs compared with B16F10 scramble-CD133(+)CD44(+) CSCs. The decrease of ZEB1 expression markedly resulted in down-regulation of vimentin and N-cadherin expression as well as up-regulation of E-cadherin expression in tumor tissues from the mice injected with B16F10 shZEB1-CD44(+)CD133(+) CSCs. These findings contribute to understanding the maintenance of B16F10 CD133(+)CD44(+) CSC-like properties that was closely associated with ZEB1 expression. ZEB1 may serve as a new therapeutic target for treatment of malignant melanoma.
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University.
authors.forename: Fengshu
authors.initials: F
authors.lastname: Zhao
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: He
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Wang
authors.forename: Fangfang
authors.initials: F
authors.lastname: Shi
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Meng
authors.initials: M
authors.lastname: Pan
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.forename: Songyan
authors.initials: S
authors.lastname: Wu
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Dou
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D018398:Homeodomain Proteins / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; C519422:ZEB1 protein, mouse; D000071799:Zinc Finger E-box-Binding Homeobox 1