Differential protein expression profiling by iTRAO-2DLC-MS/MS of lung cancer cells undergoing epithelial-mesenchymal transition reveals a migratory/invasive phenotype
Differential protein expression profiling by iTRAO-2DLC-MS/MS of lung cancer cells undergoing epithelial-mesenchymal transition reveals a migratory/invasive phenotype
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DOI：
10.1021/pr050455t
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发表时间：
2006-05-01
影响因子：
4.4
通讯作者：
Omenn, GS
中科院分区：
文献类型：
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作者：
Keshamouni, VG;Michailidis, G;Omenn, GS
在正常胚胎发育和某些病理情况下，转化生长因子-β均可诱导上皮细胞发生上皮-间充质转化。在这里，我们证明了转化生长因子-β诱导的人肺癌细胞(A549；腺癌细胞)中的EMT介导了肿瘤细胞的迁移和侵袭表型。为了深入了解EMT过程中的分子事件，我们使用了使用iTRAQ试剂的全球稳定同位素标记图谱策略，然后使用2DLC-MS/MS，鉴定了EMT过程中总共51个差异表达的蛋白质；29个蛋白质上调，22个蛋白质下调。下调的蛋白质主要是参与调节营养或药物代谢的酶。大多数由转化生长因子-β诱导的蛋白(如转孢球蛋白、细丝蛋白A、B和C、整合素-β1、热休克蛋白27、谷氨酰胺转氨酶2、Cofilin、14-3-3 Zeta、Ezrin-Radisin-moesin)参与调节细胞的迁移、黏附和侵袭，提示获得了侵袭性表型。
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.