Differential Protein Expression Profiling by iTRAQ−2DLC−MS/MS of Lung Cancer Cells Undergoing Epithelial-Mesenchymal Transition Reveals a Migratory/Invasive Phenotype

Transforming growth factor-β (TGF-β) induces epithelial-mesenchymal transition (EMT) of epithelial cells in both normal embryonic development and certain pathological contexts. Here, we show that TGF-β induced-EMT in human lung cancer cells (A549; adenocarcinoma cells) mediates tumor cell migration...

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Bibliographic Details
Published in:Journal of proteome research 2006-05, Vol.5 (5), p.1143-1154
Main Authors: Keshamouni, Venkateshwar G, Michailidis, George, Grasso, Catherine S, Anthwal, Shalini, Strahler, John R, Walker, Angela, Arenberg, Douglas A, Reddy, Raju C, Akulapalli, Sudhakar, Thannickal, Victor J, Standiford, Theodore J, Andrews, Philip C, Omenn, Gilbert S
Format: Article
Language:English
Subjects:
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
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Summary:Transforming growth factor-β (TGF-β) induces epithelial-mesenchymal transition (EMT) of epithelial cells in both normal embryonic development and certain pathological contexts. Here, we show that TGF-β 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-β-induced proteins (such as tropomyosins, filamin A, B, & C, integrin-β1, 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-β • lung cancer • epithelial-mesenchymal transitions • cell-migration • filamin • transglutaminase • HSPB1 • β1-integrin
ISSN:1535-3893
1535-3907
DOI:10.1021/pr050455t