CTP synthase forms the cytoophidium in human hepatocellular carcinoma

Exp Cell Res. 2017 Dec 15;361(2):292-299. doi: 10.1016/j.yexcr.2017.10.030. Epub 2017 Oct 31.

Abstract

CTP synthase (CTPS) can aggregate into an intracellular macrostructure, the cytoophidium, in various organisms including human cells. Previous studies have shown that assembly of human CTPS cytoophidia may be correlated with the cellular metabolic status, and is able to promote the activity of CTPS. A correlation between the cytoophidium and cancer metabolism has been proposed but not yet been revealed. In the current study we provide clear evidence of the presence of CTPS cytoophidia in various human cancers and some non-cancerous tissues. Moreover, among 203 tissue samples of hepatocellular carcinoma, 56 (28%) samples exhibited many cytoophidia, whereas no cytoophidia were detected in adjacent non-cancerous hepatocytes for all samples. Our findings suggest that the CTPS cytoophidium may participate in the adaptive metabolism of human hepatocellular carcinoma.

Keywords: CTP synthase; Cytoophidium; Glutamine metabolism; Heatshock protein 90; Human hepatocellular carcinoma; Nucleotide; Protein filamentation; Pyrimidine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carbon-Nitrogen Ligases / chemistry
  • Carbon-Nitrogen Ligases / genetics*
  • Carbon-Nitrogen Ligases / metabolism
  • Carcinoma, Hepatocellular / chemistry*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Female
  • Gene Expression
  • HSP90 Heat-Shock Proteins / genetics
  • HSP90 Heat-Shock Proteins / metabolism
  • Hepatocytes / chemistry
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Liver Neoplasms / chemistry*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Protein Aggregates*

Substances

  • HSP90 Heat-Shock Proteins
  • Neoplasm Proteins
  • Protein Aggregates
  • Carbon-Nitrogen Ligases
  • CTP synthetase