1. Constitutive expression of Wnt/β-catenin target genes promotes proliferation and invasion of liver cancer stem cells
- Author
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Qi Zhang, Tong Zhang, Jian‑Wen Zhang, Nan Jiang, Bin‑Sheng Fu, Yang Li, Wei Chen, and Yu‑Wei Zhang
- Subjects
Male ,cancer stem cells ,0301 basic medicine ,Cancer Research ,Beta-catenin ,cyclin D1 ,Antineoplastic Agents ,Mice, SCID ,Biochemistry ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Side population ,Cell Movement ,Mice, Inbred NOD ,Cancer stem cell ,Tumor Cells, Cultured ,Genetics ,AXIN2 ,Animals ,Humans ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,Side-Population Cells ,Wnt Signaling Pathway ,Molecular Biology ,beta Catenin ,Cell Proliferation ,Wnt/β-catenin ,drug resistance ,biology ,Liver Neoplasms ,Wnt signaling pathway ,LRP6 ,LRP5 ,Articles ,Middle Aged ,Up-Regulation ,Cell biology ,Wnt Proteins ,anticancer drugs ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Catenin ,Neoplastic Stem Cells ,biology.protein ,Molecular Medicine ,Female - 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.
- Published
- 2016