ZBP-89 negatively regulates self-renewal of liver cancer stem cells via suppression of Notch1 signaling pathway.
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Authors
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Wang, Nuozhou1
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Li, Ming-Yue2
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Liu, Yi3
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Yu, Jianqing1
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Ren, Jianwei1
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Zheng, Zhiyuan1
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Wang, Shanshan4
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Yang, Shucai5
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Yang, Sheng-Li6
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Liu, Li-Ping7
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Hu, Bao-Guang8
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Chong, Charing Cn1
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Merchant, Juanita L9
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Lai, Paul Bs10
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Chen, George Gong11
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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.
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(China)
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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.
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(China)
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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.
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(China)
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4
School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
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(China)
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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.
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(China)
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6
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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(China)
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7
Department of Hepatobiliary and Pancreas Surgery, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong Province, China.
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(China)
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8
Department of Gastrointestinal Surgery, The Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, China.
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(China)
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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.
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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]
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(China)
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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]
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(China)
- Type
- Published Article
- Journal
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Cancer letters
- Publication Date
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Mar 01, 2020
- Volume
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472
- Pages
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70–80
- Identifiers
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DOI: 10.1016/j.canlet.2019.12.026
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PMID: 31874246
- Source
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Medline
- Keywords
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- Language
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English
- License
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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.
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
This record was last updated on 08/13/2020 and may not reflect the most current and accurate biomedical/scientific data available from NLM.
The corresponding record at NLM can be accessed at
https://www.ncbi.nlm.nih.gov/pubmed/31874246
