Peroxiredoxin-2 represses melanoma metastasis by increasing E-cadherin/β-catenin complexes in adherens junctions

Doo Jae Lee, Dong Hoon Kang, Mina Choi, Yang Ji Choi, Joo Young Lee, Joo Hyun Park, Yoon Jung Park, Kyung Wha Lee, Sang Won Kang

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

In melanoma, transition to the vertical growth phase is the critical step in conversion to a deadly malignant disease. Here, we offer the first evidence that an antioxidant enzyme has a key role in this transition.Wefound that the antioxidant enzyme peroxiredoxin-2 (Prx2) inversely correlated with the metastatic capacity of human melanoma cells. Silencing Prx2 expression stimulated proliferation and migration, whereas ectopic expression of Prx2 produced the opposite effect. Mechanistic investigations indicated that Prx2 negatively regulated Src/ERK activation status, which in turn fortified adherens junctions function by increasing E-cadherin expression and phospho-Y654- dependent retention of β-catenin in the plasma membrane. In murine melanoma cells, Prx2 silencing enhanced lung metastasis in vivo. Interestingly, the natural compound gliotoxin, which is known to exert a Prx-like activity, inhibited proliferation and migration as well as lung metastasis of Prx2-deficient melanoma cells. Overall, our findings reveal that Prx2 is a key regulator of invasion and metastasis in melanoma, and also suggest a pharmacologic strategy to effectively decrease deadly malignant forms of this disease.

Original languageEnglish
Pages (from-to)4744-4757
Number of pages14
JournalCancer Research
Volume73
Issue number15
DOIs
StatePublished - 1 Aug 2013

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