title: Y-box binding protein-1 promotes hepatocellular carcinoma-initiating cell progression and tumorigenesis via Wnt/β-catenin pathway.
abstract: Y-box binding protein-1 (YB-1) is a pleiotropic molecule that binds DNA to regulate genes on a transcriptional level in the nucleus and binds RNA to modulate gene translation in the cytoplasm. In our previous studies, YB-1 was also characterized as a fetal hepatic protein that regulates the maturation of hepatocytes and is upregulated during liver regeneration. Moreover, YB-1 has been shown to be expressed in human hepatocellular carcinoma (HCC). However, the role of YB-1 in HCC remains unclear. Here, we aimed to characterize the role of YB-1 in HCC. Based on the results of loss-of-function in HCC and gain-of-function in mice liver using hydrodynamic gene delivery, YB-1 promoted hepatic cells proliferation in vitro and in vivo. YB-1 was also involved in HCC cell proliferation, migration, and drug-resistance. The results of extreme limiting dilution sphere forming analysis and cancer initiating cell marker analysis were also shown that YB-1 maintained HCC initiating cells population. YB-1 also induced the epithelial-mesenchymal transition and stemness-related gene expression. Knockdown of YB-1 suppressed the expression of Wnt ligands and β-catenin, impaired Wnt/β-catenin signaling pathway and reduced the numbers of HCC initiating cells. Moreover, YB-1 displayed nuclear localization particularly in the HCC initiating cells, the EpCAM+ cells or sphere cells. Our findings suggested that YB-1 was a key factor in HCC tumorigenesis and maintained the HCC initiating cell population.
authors.affiliation: niChe Laboratory for Stem Cell and Regenerative Medicine, Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan.|Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hsiao-Mei
authors.initials: HM
authors.lastname: Chao
authors.affiliation: niChe Laboratory for Stem Cell and Regenerative Medicine, Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan.
authors.forename: Hong-Xuan
authors.initials: HX
authors.lastname: Huang
authors.affiliation: niChe Laboratory for Stem Cell and Regenerative Medicine, Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan.
authors.forename: Po-Hsiang
authors.initials: PH
authors.lastname: Chang
authors.affiliation: niChe Laboratory for Stem Cell and Regenerative Medicine, Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan.
authors.forename: Kuo-Chang
authors.initials: KC
authors.lastname: Tseng
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyajima
authors.affiliation: niChe Laboratory for Stem Cell and Regenerative Medicine, Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan.
authors.forename: Edward
authors.initials: E
authors.lastname: Chern
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D016019:Survival Analysis; D060449:Wnt Signaling Pathway; D051840:Y-Box-Binding Protein 1 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human
keywords: HCC; Wnt; Y-box binding protein 1; stemness; tumor-initiating cell