ZBP-89 negatively regulates self-renewal of liver cancer stem cells via suppression of Notch1 signaling pathway
Chong, Charing Cn
Merchant, Juanita L
Lai, Paul Bs
Chen, George Gong
AffiliationUniv Arizona, Coll Med, Div Gastroenterol & Hepatol
MetadataShow full item record
PublisherELSEVIER IRELAND LTD
CitationWang, N., Li, M. Y., Liu, Y., Yu, J., Ren, J., Zheng, Z., ... & Hu, B. G. (2020). ZBP-89 negatively regulates self-renewal of liver cancer stem cells via suppression of Notch1 signaling pathway. Cancer Letters, 472, 70-80.
RightsCopyright © 2019 Elsevier B.V. All rights reserved.
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AbstractLiver cancer stem cells (LCSCs) initiate hepatocellular carcinoma (HCC) and contribute to its recurrence and treatment resistance. Studies have suggested ZBP-89 as a candidate tumor suppressor in HCC. We explored the role of ZBP-89 in the regulation of LCSCs. This study was performed in liver tissue samples from 104 HCC patients, 2 cell lines and mouse tumor models. We demonstrated that ZBP-89 was weakly expressed in LCSCs. Patients with high expression of LCSC markers displayed reduced survivals and higher recurrence rates after curative surgical operation. The expression of ZBP-89 was predictive for decreased recurrence. LCSC markers were negatively correlated with ZBP-89 in HCC tissues and in enriched liver tumor spheres. The exogenous expression of ZBP-89 attenuated the tumor-sphere formation and secondary colony formation capabilities of LCSCs in vitro and tumorigenicity in vivo. Furthermore, the negative effect of ZBP-89 on cancer sternness was Notch1-dependent. Localized with Notch1 intracellular domain (NICD1) in the nucleus, ZBP-89 repressed the Notch1 signaling pathway by competitive binding to NICD1 with MAML1. Collectively, ZBP-89 negatively regulates HCC sternness via inhibiting the Notch1 signaling.
Note12 month embargo; available online 23 December 2019.
VersionFinal accepted manuscript
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