PSME3 induces epithelial-mesenchymal transition with inducing the expression of CSC markers and immunosuppression in breast cancer

Exp Cell Res. 2017 Sep 15;358(2):87-93. doi: 10.1016/j.yexcr.2017.05.017. Epub 2017 May 19.

Abstract

Proteasome activator subunit 3 (PSME3) plays a key role in breast cancer by regulating the cell cycle. However, its role in other pathogenesis-related features of breast cancer is unclear. In this study, we found that overexpression of PSME3 induced the epithelial-mesenchymal transition and contributed to induce the expression of cancer stem cell markers of the MDA-MB-231 cell line, thus increasing the migration, and invasion of the cells. Moreover, overexpression of PSME3 reduced the chemotaxis of CD8+ T cells and induced the apoptosis of T cells in vitro. Furthermore, PSME3 knockdown increased the number of CD8+ T cells in vivo and reduced the subcutaneous tumor growth rate. These findings revealed that PSME3 induces epithelial-mesenchymal transition with inducing the expression of CSC markers and influencing the tumor immune microenvironment in breast cancer.

Keywords: Cancer stem cell markers; Epithelial–mesenchymal transition; Immune microenvironment; PSME3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantigens / genetics
  • Autoantigens / metabolism*
  • Biomarkers / metabolism
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Epithelial-Mesenchymal Transition / physiology
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Knockdown Techniques
  • Humans
  • Neoplasm Invasiveness
  • Neoplastic Stem Cells / metabolism*
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism*
  • Tumor Microenvironment / physiology*

Substances

  • Autoantigens
  • Biomarkers
  • Ki antigen
  • Proteasome Endopeptidase Complex