Human peroxiredoxin 1 modulates TGF-β1-induced epithelial-mesenchymal transition through its peroxidase activity

被引:38
作者
Ha, Bin [1 ]
Kim, Eun-Kyung [1 ]
Kim, Ji-Hee [1 ]
Lee, Hae Na [1 ]
Lee, Kyun Oh [2 ]
Lee, Sang Yeol [2 ]
Jang, Ho Hee [1 ]
机构
[1] Gachon Univ, Lee Gil Ya Canc & Diabet Inst, Inchon 406799, South Korea
[2] Gyeongsang Natl Univ, Div Appl Life Sci, Brain Korea Program 21, Jinju 660701, South Korea
基金
新加坡国家研究基金会;
关键词
hPrx1; TGF-beta; 1; Epithelial-mesenchymal transition; E-cadherin; Peroxidase activity; EPIDERMAL-GROWTH-FACTOR; CELL LUNG-CANCER; I EXPRESSION; GENE-PRODUCT; TGF-BETA; INHIBITION; DISEASE; DETERMINANT; SENSITIVITY; PROTEIN;
D O I
10.1016/j.bbrc.2012.03.103
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The epithelial-to-mesenchymal transition (EMT), which is induced by transforming growth factor-beta 1 (TGF-beta 1), is an important event that allows cancer cells to obtain invasive and metastatic characteristics. Although human peroxiredoxin 1 (hPrx1) has been implicated in tumor progression (e.g., invasion and metastasis), little is known about the role of hPrx1 in the EMT process during tumorigenesis. Here, we investigated the regulatory effect of hPrx1 during TGF-beta 1-induced EMT in A549 lung adenocarcinoma cells. We observed that high hPrx1 levels downregulated E-cadherin expression, and low hPrx1 levels upregulated E-cadherin expression, suggesting that the hPrx1 level may be correlated with EMT. Knockdown of hPrx1 significantly inhibited TGF-beta 1-induced EMT and cell migration, whereas hPrx1 overexpression enhanced TGF-beta 1-induced EMT and cell migration. In contrast to wild-type hPrx1, a peroxidase-inactive hPrx1 mutant (hPrx1-C51S) resulted in markedly increased E-cadherin expression. Moreover, hPrx1 regulated the expression of two E-cadherin transcriptional repressors, Snail and Slug. These findings provide new insight into the role of hPrx1 in regulating TGF-beta 1-induced EMT. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:33 / 37
页数:5
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