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-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.
Keshamouni
Venkateshwar G
VG
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
Michailidis
George
G
Grasso
Catherine S
CS
Anthwal
Shalini
S
Strahler
John R
JR
Walker
Angela
A
Arenberg
Douglas A
DA
Reddy
Raju C
RC
Akulapalli
Sudhakar
S
Thannickal
Victor J
VJ
Standiford
Theodore J
TJ
Andrews
Philip C
PC
Omenn
Gilbert S
GS