Differential protein expression profiling by iTRAQ-2DLC-MS/MS of lung cancer cells undergoing epithelial-mesenchymal transition reveals a migratory/invasive phenotype

J Proteome Res. 2006 May;5(5):1143-54. doi: 10.1021/pr050455t.


Transforming growth factor-beta (TGF-beta) induces epithelial-mesenchymal transition (EMT) of epithelial cells in both normal embryonic development and certain pathological contexts. Here, we show that TGF-beta induced-EMT in human lung cancer cells (A549; adenocarcinoma cells) mediates tumor cell migration and invasion phenotypes. To gain insights into molecular events during EMT, we employed a global stable isotope labeled profiling strategy using iTRAQ reagents, followed by 2DLC-MS/MS, which identified a total of 51 differentially expressed proteins during EMT; 29 proteins were up-regulated and 22 proteins were down-regulated. Down-regulated proteins were predominantly enzymes involved in regulating nutrient or drug metabolism. The majority of the TGF-beta-induced proteins (such as tropomyosins, filamin A, B, & C, integrin-beta1, heat shock protein27, transglutaminase2, cofilin, 14-3-3 zeta, ezrin-radixin-moesin) are involved in the regulation of cell migration, adhesion and invasion, suggesting the acquisition of a invasive phenotype.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / pathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Chromatography, Liquid / methods
  • Epithelial Cells / pathology
  • Humans
  • Image Processing, Computer-Assisted
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology*
  • Mass Spectrometry / methods*
  • Mesoderm / pathology
  • Neoplasm Invasiveness
  • Phenotype
  • Proteins / analysis*
  • Proteins / drug effects
  • Proteins / metabolism
  • Proteomics / methods*
  • Software
  • Transforming Growth Factor beta / pharmacology


  • Proteins
  • Transforming Growth Factor beta