Degradation of AZGP1 suppresses the progression of breast cancer cells via TRIM25

Environ Toxicol. 2024 Feb;39(2):882-889. doi: 10.1002/tox.24016. Epub 2023 Nov 6.

Abstract

Alpha-2-glycoprotein 1, zinc-binding (AZGP1) is a secreted protein, which has been shown to be a potential biomarker of cancer progression; however, its roles in breast cancer are still unclear. Currently, we analyzed the online datasets and found that AZGP1 was highly expressed in breast cancer tissues and its expression was negatively correlated with the survival of breast cancer patients. Functional experiments through AZGP1 knockdown revealed that AZGP1 could promote the proliferation, migration, and invasion ability of breast cancer cells. In vivo experiments obtained a consistent result. Mechanistically, it was found that AZGP1 interacted with tripartite motif-containing protein 25 (TRIM25), which subsequently promoted AZGP1 degradation through facilitating the ubiquitination. Furthermore, overexpression of TRIM25 partially reversed the promoting effects of AZGP1 overexpression on breast cancer progression. Therefore, this study indicates that AZGP1 might be a potential therapeutic target for breast cancer treatment.

Keywords: AZGP1; TRIM25; breast cancer; degradation; ubiquitination.

MeSH terms

  • Adipokines
  • Breast Neoplasms* / genetics
  • Female
  • Glycoproteins / metabolism
  • Humans
  • Transcription Factors
  • Tripartite Motif Proteins / genetics
  • Ubiquitin-Protein Ligases / genetics
  • Zn-Alpha-2-Glycoprotein

Substances

  • Adipokines
  • Glycoproteins
  • TRIM25 protein, human
  • Tripartite Motif Proteins
  • Transcription Factors
  • Ubiquitin-Protein Ligases
  • AZGP1 protein, human
  • Zn-Alpha-2-Glycoprotein