Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-799, Republic of Korea.
Biochem Biophys Res Commun. 2012 Apr 27;421(1):33-7. doi: 10.1016/j.bbrc.2012.03.103. Epub 2012 Mar 27.
The epithelial-to-mesenchymal transition (EMT), which is induced by transforming growth factor-β1 (TGF-β1), 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-β1-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-β1-induced EMT and cell migration, whereas hPrx1 overexpression enhanced TGF-β1-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-β1-induced EMT.
上皮间质转化（EMT）是由转化生长因子-β1（TGF-β1）诱导的，是使癌细胞获得侵袭和转移特性的重要事件。虽然人类过氧化物酶 1（hPrx1）已被牵连到肿瘤进展（例如侵袭和转移）中，但关于 hPrx1 在肿瘤发生过程中的 EMT 中的作用知之甚少。在这里，我们研究了 hPrx1 在 A549 肺腺癌细胞中 TGF-β1 诱导的 EMT 过程中的调节作用。我们观察到高 hPrx1 水平下调 E-钙粘蛋白的表达，而低 hPrx1 水平上调 E-钙粘蛋白的表达，这表明 hPrx1 水平可能与 EMT 相关。hPrx1 的敲低显著抑制 TGF-β1 诱导的 EMT 和细胞迁移，而 hPrx1 的过表达增强 TGF-β1 诱导的 EMT 和细胞迁移。与野生型 hPrx1 相比，过氧化物酶失活的 hPrx1 突变体（hPrx1-C51S）导致 E-钙粘蛋白的表达明显增加。此外，hPrx1 调节了两种 E-钙粘蛋白转录阻遏物 Snail 和 Slug 的表达。这些发现为 hPrx1 在调节 TGF-β1 诱导的 EMT 中的作用提供了新的见解。
