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.
| Original language | English |
|---|---|
| Pages (from-to) | 2604-2616 |
| Number of pages | 13 |
| Journal | Oncotarget |
| Volume | 8 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jan 1 2017 |
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Keywords
- HCC
- Stemness
- Tumor-initiating cell
- Wnt
- Y-box binding protein 1
ASJC Scopus subject areas
- Oncology
Cite this
Y-box binding protein-1 promotes hepatocellular carcinoma-initiating cell progression and tumorigenesis via Wnt/β-catenin pathway. / Chao, Hsiao Mei; Huang, Hong Xuan; Chang, Po Hsiang; Tseng, Kuo Chang; Miyajima, Atsushi; Chern, Edward.
In: Oncotarget, Vol. 8, No. 2, 01.01.2017, p. 2604-2616.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Y-box binding protein-1 promotes hepatocellular carcinoma-initiating cell progression and tumorigenesis via Wnt/β-catenin pathway
AU - Chao, Hsiao Mei
AU - Huang, Hong Xuan
AU - Chang, Po Hsiang
AU - Tseng, Kuo Chang
AU - Miyajima, Atsushi
AU - Chern, Edward
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - HCC
KW - Stemness
KW - Tumor-initiating cell
KW - Wnt
KW - Y-box binding protein 1
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UR - http://www.scopus.com/inward/citedby.url?scp=85009754312&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.13733
DO - 10.18632/oncotarget.13733
M3 - Article
VL - 8
SP - 2604
EP - 2616
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 2
ER -