title: Peroxiredoxin-2 represses melanoma metastasis by increasing E-Cadherin/β-Catenin complexes in adherens junctions.
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. 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 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.
authors.affiliation: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Doo Jae
authors.initials: DJ
authors.lastname: Lee
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Kang
authors.forename: Mina
authors.initials: M
authors.lastname: Choi
authors.forename: Yang Ji
authors.initials: YJ
authors.lastname: Choi
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Yoon Jung
authors.initials: YJ
authors.lastname: Park
authors.forename: Kyung Wha
authors.initials: KW
authors.lastname: Lee
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Kang
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness / Q000473:pathology*; D054464:Peroxiredoxins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015820:Cadherins; D051176:beta Catenin; D054464:Peroxiredoxins