Web Release Date: March 24,
Differential Protein Expression Profiling by iTRAQ-2DLC-MS/MS of Lung Cancer Cells Undergoing Epithelial-Mesenchymal Transition Reveals a Migratory/Invasive Phenotype
and
Divisions of Pulmonary and Critical Care Medicine and Molecular Medical Genetics, Department of Internal Medicine, Michigan Proteomics Consortium, National Resource for Proteomics and Pathways, and Department of Biological Chemistry, Department of Statistics, and Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, 48109, and Cell Signaling and Angiogenesis Laboratory, Boys Town National Research Hospital, University of Nebraska Medical Center, Omaha, Nebraska 68131
Received December 12, 2005
Abstract:
Transforming growth factor-
(TGF-) induces epithelial-mesenchymal transition (EMT) of epithelial
cells in both normal embryonic development and certain pathological contexts. Here, we show that
TGF- 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--induced proteins (such as
tropomyosins, filamin A, B, & C, integrin-1, 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.
Keywords: iTRAQ 
quantitative proteomics TGF- lung cancer epithelial-mesenchymal transitions
cell-migration filamin transglutaminase HSPB1 1-integrin
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