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Citations to this article

ZIC2-dependent OCT4 activation drives self-renewal of human liver cancer stem cells
Pingping Zhu, … , Jiayi Wu, Zusen Fan
Pingping Zhu, … , Jiayi Wu, Zusen Fan
Published August 31, 2015
Citation Information: J Clin Invest. 2015;125(10):3795-3808. https://doi.org/10.1172/JCI81979.
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Research Article Oncology Article has an altmetric score of 1

ZIC2-dependent OCT4 activation drives self-renewal of human liver cancer stem cells

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Abstract

Liver cancer stem cells (CSCs) have been identified and shown to have self-renewal and differentiation properties; however, the biology of these hepatic CSCs remains largely unknown. Here, we analyzed transcriptome gene expression profiles of liver CSCs and non-CSCs from hepatocellular carcinoma (HCC) cells lines and found that the transcription factor (TF) ZIC2 is highly expressed in liver CSCs. ZIC2 was required for the self-renewal maintenance of liver CSCs, as ZIC2 depletion reduced sphere formation and xenograft tumor growth in mice. We determined that ZIC2 acts upstream of the TF OCT4 and that ZIC2 recruits the nuclear remodeling factor (NURF) complex to the OCT4 promoter, thereby initiating OCT4 activation. In HCC patients, expression levels of the NURF complex were consistent with clinical severity and prognosis. Moreover, ZIC2 and OCT4 levels positively correlated to the clinicopathological stages of HCC patients. Altogether, our results indicate that levels of ZIC2, OCT4, and the NURF complex can be detected and used for diagnosis and prognosis prediction of HCC patients. Moreover, these factors may be potential therapeutic targets for eradicating liver CSCs.

Authors

Pingping Zhu, Yanying Wang, Lei He, Guanling Huang, Ying Du, Geng Zhang, Xinlong Yan, Pengyan Xia, Buqing Ye, Shuo Wang, Lu Hao, Jiayi Wu, Zusen Fan

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2009 Total
Citations: 3 6 6 11 11 13 10 15 12 3 1 1 92
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2016 (3)

Title and authors Publication Year
LncSox4 promotes the self-renewal of liver tumour-initiating cells through Stat3-mediated Sox4 expression
Z Chen, L Huang, Y Wu, W Zhai, P Zhu, Y Gao
Nature Communications 2016
LncBRM initiates YAP1 signalling activation to drive self-renewal of liver cancer stem cells
P Zhu, Y Wang, J Wu, G Huang, B Liu, B Ye, Y Du, G Gao, Y Tian, L He, Z Fan
Nature Communications 2016
lnc-β-Catm elicits EZH2-dependent β-catenin stabilization and sustains liver CSC self-renewal
P Zhu, Y Wang, G Huang, B Ye, B Liu, J Wu, Y Du, L He, Z Fan
Nature Structural & Molecular Biology 2016

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