title: Constitutive expression of Wnt/β‑catenin target genes promotes proliferation and invasion of liver cancer stem cells.
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.
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Zhang
authors.affiliation: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Jian-Wen
authors.initials: JW
authors.lastname: Zhang
authors.affiliation: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Bin-Sheng
authors.initials: BS
authors.lastname: Fu
authors.affiliation: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002465:Cell Movement; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*; D058985:Side-Population Cells / Q000166:cytology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1