Defective mitosis-linked DNA damage response and chromosomal instability in liver cancer

Biochim Biophys Acta Rev Cancer. 2019 Aug;1872(1):60-65. doi: 10.1016/j.bbcan.2019.05.008. Epub 2019 May 29.

Abstract

Hepatocellular carcinoma (HCC), the most common form of liver cancer, represents a health problem in hepatic viruses-eradicating era because obesity, type 2 diabetes, and nonalcoholic steatohepatitis (NASH) are considered emerging pathogenic factors. Metabolic disorders underpin mitotic errors that lead to numerical and structural chromosome aberrations in a significant proportion of cell divisions. Here, we review that genomically unstable HCCs show evidence for a paradoxically DNA damage response (DDR) which leads to ongoing chromosome segregation errors. The understanding of DDR induced by defective mitoses is crucial to our ability to develop or improve liver cancer therapeutic strategies.

Keywords: Aneuploidy; Chromosome abnormalities; DNA damage checkpoint; Defective chromosome segregations; Hepatocellular carcinoma; Mitotic checkpoint.

Publication types

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

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Chromosomal Instability / genetics
  • Chromosome Segregation / genetics
  • DNA Damage / genetics
  • Genome, Human / genetics*
  • Genomic Instability / genetics*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Mitosis / genetics