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

被引:226
作者
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
机构
[1] Univ Michigan, Med Ctr, Dept Internal Med,Natl Resource Proteom & Pathway, Div Pulm & Crit Care Med,Michigan Proteom Consort, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Med Ctr, Dept Internal Med,Natl Resource Proteom & Pathway, Div Mol Med Genet,Michigan Proteom Consortium, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA
[5] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA
[6] Univ Nebraska, Med Ctr, Cell Signaling & Angiogenesis Lab, Boys Town Natl Res Hosp, Omaha, NE 68131 USA
关键词
iTRAQ; quantitative proteomics; TGF-beta; lung cancer; epithelial-mesenchymal transitions; cell-migration; filamin; transglutaminase; HSPB1; beta; 1-integrin;
D O I
10.1021/pr050455t
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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 tropornyosins, filamin A, B, & C, integrin-beta 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.
引用
收藏
页码:1143 / 1154
页数:12
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