Core Fucosylation Is Required for the Secretion of and the Enzymatic Activity of SOD3 in Nonsmall-Cell Lung Cancer Cells

Antioxid Redox Signal. 2023 Jun;38(16-18):1201-1211. doi: 10.1089/ars.2022.0010. Epub 2023 Mar 6.

Abstract

Aims: The anticancer function of superoxide dismutases (SODs) is still controversial. SOD3 is an extracellular superoxide dismutase and contains a single N-glycan chain. The role played by the N-glycosylation of SOD3, as it relates to lung cancer, is poorly understood. For this, we performed the structural and functional analyses of the N-glycan of SOD3 in lung cancer. Results: We report herein that the fucose structure of the N-glycan in SOD3 was increased in the sera of patients with lung cancer. In cell lines of non-small lung cancer cell (NSCLC), we also found a high level of the core fucose structure in the N-glycan of SOD3, as determined by lectin blotting and mass spectrometry analysis. To address the roles of the core fucose structure of SOD3, we generated FUT8 (α1,6-fucosyltransferase) gene knockout A549 cells. Using these cells, we found that the core fucose structure of SOD3 was required for its secretion and enzymatic activity, which contributes to the suppression of cell growth of NSCLC cells. Innovation: The core fucosylation is required for the secretion and enzymatic activity of SOD3, which contributes to anti-tumor functions such as the suppression of cell growth of NSCLC. Conclusion: The N-glycans, especially those with core fucose structures, regulate the anti-tumor functions of SOD3 against NSCLC. Antioxid. Redox Signal. 38, 1201-1211.

Keywords: N-glycan; NSCLC; SOD3; core fucose.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung*
  • Fucose / metabolism
  • Fucosyltransferases / genetics
  • Fucosyltransferases / metabolism
  • Glycosylation
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Polysaccharides / chemistry
  • Polysaccharides / metabolism
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism

Substances

  • Fucose
  • Fucosyltransferases
  • Polysaccharides
  • SOD3 protein, human
  • Superoxide Dismutase