Differential protein expression profiling by iTRAQ-2DLC-MS/MS of lung cancer cells undergoing epithelial-mesenchymal transition reveals a migratory/invasive phenotype.
Keshamouni VG,
Michailidis G,
Grasso CS,
Anthwal S,
Strahler JR,
Walker A,
Arenberg DA,
Reddy RC,
Akulapalli S,
Thannickal VJ,
Standiford TJ,
Andrews PC,
Omenn GS.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Michigan Proteomics Consortium, National Resource for Proteomics and Pathways, University of Michigan, Ann Arbor, Michigan, 48109, USA. vkeshamo@med.umich.edu
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.
PMID: 16674103 [PubMed - indexed for MEDLINE]