Constitutive expression of Wnt/β‑catenin target genes promotes proliferation and invasion of liver cancer stem cells

Wnt/β‑catenin靶基因组成性表达促进肝癌干细胞增殖和侵袭

阅读:8
作者:Wei Chen, Yu-Wei Zhang, Yang Li, Jian-Wen Zhang, Tong Zhang, Bin-Sheng Fu, Qi Zhang, Nan Jiang

Abstract

Wnt/β‑catenin is an important signaling pathways involved in the tumorgenesis, progression and maintenance of cancer stem cells (CSCs). In the present study, the role of Wnt/β‑catenin signaling in CSC‑mediated tumorigenesis and invasion in liver CSCs was investigated. A small population of cancer stem‑like side population (SP) cells (3.6%) from liver cancer samples were identified. The cells were highly resistant to drug treatment due to the enhanced expression of drug efflux pumps, such as ABC subfamily G member 2, multidrug resistance protein 1 and ATP‑binding cassette subfamily B member 5. Furthermore, using TOPflash and reverse transcription‑quantitative polymerase chain reaction analysis, Wnt/β‑catenin signaling and the transcriptional regulation of Wnt/β‑catenin target genes including dickkopf Wnt signaling pathway inhibitor 1, axis inhibition protein 2 and cyclin D1 were observed to be markedly upregulated in liver cancer SP cells. As a consequence, SP cells possessed infinite cell proliferation potential and the ability to generating tumor spheres. In addition, upon reducing Wnt/β‑catenin signaling, the rates of proliferation, tumor sphere formation and tumor invasion of SP cells were markedly reduced. Therefore, these data suggest that Wnt/β‑catenin signaling is a potential therapeutic target to reduce CSC‑mediated tumorigenicity and invasion in liver cancer.

特别声明

1、本页面内容包含部分的内容是基于公开信息的合理引用;引用内容仅为补充信息,不代表本站立场。

2、若认为本页面引用内容涉及侵权,请及时与本站联系,我们将第一时间处理。

3、其他媒体/个人如需使用本页面原创内容,需注明“来源:[生知库]”并获得授权;使用引用内容的,需自行联系原作者获得许可。

4、投稿及合作请联系:info@biocloudy.com。