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

Chen,Wei; Zhang,Yu‑Wei; Li,Yang; Zhang,Jian‑Wen; Zhang,Tong; Fu,Bin‑Sheng; Zhang,Qi; Jiang,Nan

doi:10.3892/mmr.2016.4986

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

Authors:
- Wei Chen
- Yu‑Wei Zhang
- Yang Li
- Jian‑Wen Zhang
- Tong Zhang
- Bin‑Sheng Fu
- Qi Zhang
- Nan Jiang
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Affiliations: Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China, Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China, Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China
Published online on: March 7, 2016 https://doi.org/10.3892/mmr.2016.4986
Pages: 3466-3474
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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