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    ZSCAN4 facilitates chromatin remodeling and promotes the cancer stem cell phenotype

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    Author
    Portney, B.A.
    Arad, M.
    Gupta, A.
    Brown, R.A.
    Khatri, R.
    Lin, P.N.
    Hebert, A.M.
    Angster, K.H.
    Silipino, L.E.
    Meltzer, W.A.
    Taylor, R.J.
    Zalzman, M.
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    Date
    2020
    Journal
    Oncogene
    Publisher
    Springer Nature
    Type
    Article
    
    Metadata
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    See at
    https://doi.org/10.1038/s41388-020-1333-1
    Abstract
    Cancer stem cells (CSCs) are cells within tumors that maintain the ability to self-renew, drive tumor growth, and contribute to therapeutic resistance and cancer recurrence. In this study, we investigate the role of Zinc finger and SCAN domain containing 4 (ZSCAN4) in human head and neck squamous cell carcinoma (HNSCC). The murine Zscan4 is involved in telomere maintenance and genomic stability of mouse embryonic stem cells. Our data indicate that the human ZSCAN4 is enriched for, marks and is co-expressed with CSC markers in HNSCC. We show that transient ZSCAN4 induction for just 2 days increases CSC frequency both in vitro and in vivo and leads to upregulation of pluripotency and CSC factors. Importantly, we define for the first time the role of ZSCAN4 in altering the epigenetic profile and regulating the chromatin state. Our data show that ZSCAN4 leads to a functional histone 3 hyperacetylation at the promoters of OCT3/4 and NANOG, leading to an upregulation of CSC factors. Consistently, ZSCAN4 depletion leads to downregulation of CSC markers, decreased ability to form tumorspheres and severely affects tumor growth. Our study suggests that ZSCAN4 plays an important role in the maintenance of the CSC phenotype, indicating it is a potential therapeutic target in HNSCC. Copyright 2020, The Author(s).
    Keyword
    Zinc finger and SCAN domain containing 4
    cancer stem cells
    Chromatin Assembly and Disassembly
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85086022373&doi=10.1038%2fs41388-020-1333-1&partnerID=40&md5=aa669d7136960911851aab91a933da4e; http://hdl.handle.net/10713/13101
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41388-020-1333-1
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