BioScience Trends. 2015;9(5):325-334. (DOI: 10.5582/bst.2015.01106)

Decrease of ZEB1 expression inhibits the B16F10 cancer stem-like properties.

Zhao FS, He XF, Wang YQ, Shi FF, Wu D, Pan M, Li M, Wu SY, Wang XY, Dou J


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 downregulation 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+ CSClike properties that was closely associated with ZEB1 expression. ZEB1 may serve as a new therapeutic target for treatment of malignant melanoma.

KEYWORDS: Melanoma, cancer stem cells, stem-like properties, RNA interference, zinc finger E-box-binding protein 1

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