Targeting ZBP-89 for the treatment of hepatocellular carcinoma

Expert Opin Ther Targets. 2018 Oct;22(10):817-822. doi: 10.1080/14728222.2018.1516753. Epub 2018 Sep 6.

Abstract

Zinc-binding protein-89 (ZBP-89) is a Krüppel-type zinc-finger transcription factor that regulates target gene expression profiles via directly binding to GC-rich gene promoters, recruiting chromatin modifiers or by interacting with other proteins. The importance of ZBP-89 in the regulation of cell cycle arrest and apoptosis has led to increased interest and investigations for its role in cancer development. Areas covered: We describe ZBP-89 as a candidate therapeutic target for hepatocellular carcinoma (HCC) from several perspectives. ZBP-89 can upregulate apoptosis in HCC in a p53-dependent or - independent manner. In addition, the negative regulation of ZBP-89 on liver cancer stemness sheds light on its possible effect on sensitizing HCC to chemotherapies and the reduction of HCC relapse. The prognostic significance of ZBP-89 in HCC patients further suggests its clinical importance as a potential tumor suppressor. Expert opinion: Given the roles of ZBP-89 in HCC, we believe, ZBP-89 is a promising therapeutic target for enhancing apoptosis and diminishing the liver cancer stemness. At the same time, we also face a series of challenges, especially in the clinical implication of ZBP-89. Resolving the current controversies will advance the development of ZBP-89 for anti-HCC therapy.

Keywords: Apoptosis; ZBP-89; cancer stemness; hepatocellular carcinoma; transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / genetics
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Cell Cycle Checkpoints / genetics
  • DNA-Binding Proteins / genetics*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Molecular Targeted Therapy
  • Neoplasm Recurrence, Local
  • Neoplastic Stem Cells / metabolism
  • Prognosis
  • Transcription Factors / genetics*

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Transcription Factors
  • ZNF148 protein, human