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

Nuozhou Wang, Ming yue Li, Yi Liu, Jianqing Yu, Jianwei Ren, Zhiyuan Zheng, Shanshan Wang, Shucai Yang, Sheng li Yang, Li ping Liu, Bao guang Hu, Charing CN Chong, Juanita L. Merchant, Paul BS Lai, George Gong Chen

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)70-80
Number of pages11
JournalCancer Letters
Volume472
DOIs
StatePublished - Mar 1 2020
Externally publishedYes

Keywords

  • Hepatocellular carcinoma
  • Liver cancer stemness
  • Notch1
  • Recurrence
  • ZBP-89

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'ZBP-89 negatively regulates self-renewal of liver cancer stem cells via suppression of Notch1 signaling pathway'. Together they form a unique fingerprint.

Cite this