FYN promotes breast cancer progression through epithelial-mesenchymal transition

Oncol Rep. 2016 Aug;36(2):1000-6. doi: 10.3892/or.2016.4894. Epub 2016 Jun 22.

Abstract

FYN, one of the members of the Src family of kinases (SFKs), has been reported to be overexpressed in various types of cancers and correlated with cell motility and proliferation. However, the mechanism is still unclear. In the present study, we found that FYN was overexpressed in breast cancer and overexpression of FYN promoted cell proliferation, migration and invasion in the MCF10A cells, whereas depletion of FYN suppressed cell proliferation, migration and invasion in the MDA-MB-231 cells. Moreover, FYN upregulated the expression of mesenchymal markers and epithelial-mesenchymal transition (EMT)-related transcription factors, and downregulated the expression of epithelial markers, suggesting that FYN induces EMT in breast cancer cells. Furthermore, FYN was transcriptionally regulated by FOXO1 and mediated FGF2-induced EMT through both the PI3K/AKT and ERK/MAPK pathways.

MeSH terms

  • Breast / pathology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Fibroblast Growth Factor 2 / genetics
  • Forkhead Box Protein O1 / genetics
  • Humans
  • MCF-7 Cells
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Phosphatidylinositol 3-Kinases / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-fyn / genetics*
  • Signal Transduction / genetics
  • Transcription Factors / genetics
  • Up-Regulation / genetics

Substances

  • Forkhead Box Protein O1
  • Transcription Factors
  • Fibroblast Growth Factor 2
  • Phosphatidylinositol 3-Kinases
  • FYN protein, human
  • Proto-Oncogene Proteins c-fyn
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase Kinases