The Role of Irisin/FNDC5 Expression and Its Serum Level in Breast Cancer

Int J Mol Sci. 2023 May 11;24(10):8628. doi: 10.3390/ijms24108628.

Abstract

Irisin (Ir) is an adipomyokine formed from fibronectin type III domain-containing protein 5 (FNDC5), which can be found in various cancer tissues. Additionally, FNDC5/Ir is suspected of inhibiting the epithelial-mesenchymal transition (EMT) process. This relationship has been poorly studied for breast cancer (BC). The ultrastructural cellular localizations of FNDC5/Ir were examined in BC tissues and BC cell lines. Furthermore, we compared serum levels of Ir with FNDC5/Ir expression in BC tissues. The aim of this study was to examine the levels of EMT markers, such as E-cadherin, N-cadherin, SNAIL, SLUG, and TWIST, and to compare their expression levels with FNDC5/Ir in BC tissues. Tissue microarrays with 541 BC samples were used to perform immunohistochemical reactions. Serum levels of Ir were assessed in 77 BC patients. We investigated FNDC5/Ir expression and ultrastructural localization in MCF-7, MDA-MB-231, and MDA-MB-468 BC cell lines and in the normal breast cell line (Me16c), which was used as the control. FNDC5/Ir was present in BC cell cytoplasm and tumor fibroblasts. FNDC5/Ir expression levels in BC cell lines were higher compared to those in the normal breast cell line. Serum Ir levels did not correlate with FNDC5/Ir expression in BC tissues but were associated with lymph node metastasis (N) and histological grade (G). We found that FNDC5/Ir correlated moderately with E-cadherin and SNAIL. Higher Ir serum level is associated with lymph node metastasis and increased grade of malignancy. FNDC5/Ir expression is associated with E-cadherin expression level.

Keywords: E-cadherin; EMT; FNDC5; SLUG; SNAIL; TWIST; breast cancer (BC); irisin.

MeSH terms

  • Breast Neoplasms* / metabolism
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition
  • Female
  • Fibronectins
  • Humans
  • Lymphatic Metastasis
  • Transcription Factors / metabolism

Substances

  • Fibronectins
  • Transcription Factors
  • Cadherins
  • FNDC5 protein, human