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ZBP-89 negatively regulates self-renewal of liver cancer stem cells via suppression of Notch1 signaling pathway.

Authors
  • Wang, Nuozhou1
  • Li, Ming-Yue2
  • Liu, Yi3
  • Yu, Jianqing1
  • Ren, Jianwei1
  • Zheng, Zhiyuan1
  • Wang, Shanshan4
  • Yang, Shucai5
  • Yang, Sheng-Li6
  • Liu, Li-Ping7
  • Hu, Bao-Guang8
  • Chong, Charing Cn1
  • Merchant, Juanita L9
  • Lai, Paul Bs10
  • Chen, George Gong11
  • 1 Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China. , (China)
  • 2 Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, Guangdong, China. , (China)
  • 3 Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong, China. , (China)
  • 4 School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China. , (China)
  • 5 Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Department of Clinical Laboratory, Pingshan District People's Hospital of Shenzhen, Shenzhen, Guangdong, China. , (China)
  • 6 Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. , (China)
  • 7 Department of Hepatobiliary and Pancreas Surgery, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong Province, China. , (China)
  • 8 Department of Gastrointestinal Surgery, The Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, China. , (China)
  • 9 Division of Gastroenterology, Division of Gastroenterology & Hepatology, University of Arizona College of Medicine, PO Box 245028, 1501 N. Campbell Ave, Tucson, AZ, 85724-5028, USA.
  • 10 Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: [email protected] , (China)
  • 11 Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, Guangdong, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Cancer letters
Publication Date
Mar 01, 2020
Volume
472
Pages
70–80
Identifiers
DOI: 10.1016/j.canlet.2019.12.026
PMID: 31874246
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Liver 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 stemness 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 stemness via inhibiting the Notch1 signaling. Copyright © 2019 Elsevier B.V. All rights reserved.

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