Peroxiredoxin-2 represses melanoma metastasis by increasing E-cadherin/β-catenin complexes in adherens junctions
Menée in vitro et in vivo, cette étude met en évidence le rôle joué par l'enzyme Prx2 dans la régulation des processus invasif et métastatique d'un mélanome
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. We found 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 Prx2 as a key regulator of invasion and metastasis in melanoma, and they also suggest a pharmacological strategy to effectively deadly malignant forms of this disease.