title: Human peroxiredoxin 1 modulates TGF-β1-induced epithelial-mesenchymal transition through its peroxidase activity.
abstract: 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.
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-799, Republic of Korea.
authors.forename: Bin
authors.initials: B
authors.lastname: Ha
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.forename: Ji-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Hae Na
authors.initials: HN
authors.lastname: Lee
authors.forename: Kyun Oh
authors.initials: KO
authors.lastname: Lee
authors.forename: Sang Yeol
authors.initials: SY
authors.lastname: Lee
authors.forename: Ho Hee
authors.initials: HH
authors.lastname: Jang
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D015820:Cadherins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; C515940:PRDX1 protein, human; D054464:Peroxiredoxins; D009195:Peroxidase