Transforming growth factor-β1 induces epithelial-mesenchymal transition and integrin α3β1-mediated cell migration of HSC-4 human squamous cell carcinoma cells through Slug

J Biochem. 2013 Mar;153(3):303-15. doi: 10.1093/jb/mvs144. Epub 2012 Dec 17.


We investigated whether transforming growth factor (TGF)-β1 promoted epithelial-mesenchymal transition (EMT) and migration of human oral squamous cell carcinoma (hOSCC) cells. Among 6 hOSCC cell lines investigated, Smad2 phosphorylation and TGF-β target genes expression were most clearly upregulated following TGF-β1 stimulation in HSC-4 cells, indicating that HSC-4 cells were the most responsive to TGF-β1. In addition, the expression levels of the mesenchymal markers N-cadherin and vimentin were most clearly induced in HSC-4 cells among the hOSCC cell lines by TGF-β1 stimulation. Interestingly, E-cadherin and β-catenin at the cell surface were internalized in HSC-4 cells stimulated with TGF-β1. In addition, the expression levels of the EMT-related transcription factor Slug was significantly upregulated on TGF-β1 stimulation. Moreover, the downregulation of Slug by RNA interference clearly inhibited the TGF-β1-induced expression of mesenchymal marker and the migration of HSC-4 cells. Proteomics analysis also revealed that the expression levels of integrin α3β1-targeted proteins were upregulated in TGF-β1-stimulated HSC-4 cells. Neutral antibodies against integrin α3 and β1, as well as a focal adhesion kinase (FAK) inhibitor, clearly suppressed TGF-β1-induced cell migration. These results suggest that the EMT and integrin α3β1/FAK pathway-mediated migration of TGF-β1-stimulated HSC-4 hOSCC cells is positively controlled by Slug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cadherins / genetics
  • Cadherins / metabolism
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Movement / genetics
  • Epithelial-Mesenchymal Transition / drug effects*
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Integrin alpha3beta1 / genetics
  • Integrin alpha3beta1 / metabolism*
  • Microscopy, Confocal
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Smad7 Protein / genetics
  • Smad7 Protein / metabolism
  • Snail Family Transcription Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transforming Growth Factor beta1 / pharmacology*


  • Cadherins
  • Integrin alpha3beta1
  • SMAD7 protein, human
  • SNAI1 protein, human
  • Smad7 Protein
  • Snail Family Transcription Factors
  • Transcription Factors
  • Transforming Growth Factor beta1