High expression of glutamate-ammonia ligase is associated with unfavorable prognosis in patients with ovarian cancer

J Cell Biochem. 2018 Jul;119(7):6008-6015. doi: 10.1002/jcb.26797. Epub 2018 Mar 25.

Abstract

Glutamate-ammonia ligase (GLUL), which is also called GS (glutamine synthetase), is the enzyme that catalyzes the synthesis of glutamine from glutamate and ammonia in an ATP-dependent reaction. Here, we found higher expression of GLUL in the ovarian cancer patients was associated with worse disease-free survival (DFS) and overall survival (OS). In addition, GLUL was heterogeneously expressed in various ovarian cancer cells. The mRNA and protein expression levels of GLUL in NIH:OVCAR-3 and ES-2 cells were obviously higher than that in the other types of ovarian cancer cells. Knockdown of GLUL in NIH:OVCAR-3 or ES-2 cells could significantly decrease the proliferation ability. Furthermore, GLUL knockdown markedly inhibited the p38 MAPK signaling pathway in NIH:OVCAR-3 or ES-2 cells. Our findings suggest that decreasing expression of GLUL may be a new approach that can be used for ovarian cancer treatment.

Keywords: glutamate-ammonia ligase; ovarian cancer; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Clear Cell / enzymology
  • Adenocarcinoma, Clear Cell / pathology
  • Adenocarcinoma, Mucinous / enzymology
  • Adenocarcinoma, Mucinous / pathology
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation
  • Cystadenocarcinoma, Serous / enzymology
  • Cystadenocarcinoma, Serous / pathology
  • Endometrial Neoplasms / enzymology
  • Endometrial Neoplasms / pathology
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Glutamate-Ammonia Ligase / metabolism*
  • Humans
  • Middle Aged
  • Neoplasm Invasiveness
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • Survival Rate
  • Tumor Cells, Cultured
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Biomarkers, Tumor
  • p38 Mitogen-Activated Protein Kinases
  • GLUL protein, human
  • Glutamate-Ammonia Ligase