Related Experiment Video
Updated: Jun 22, 2025

Monitoring On-Target Signaling Responses in Larval Zebrafish - Z-REX Unmasks Precise Mechanisms of Electrophilic Drugs and Metabolites
Published on: June 2, 2023
Peroxiredoxin-2 represses NRAS-mutated melanoma cells invasion by modulating EMT markers
Isabella Harumi Yonehara Noma1, Larissa Anastacio da Costa Carvalho1, Denisse Esther Mallaupoma Camarena1
1Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes, 580, São Paulo, SP 05508-00, Brazil.
Abstract:
The second most common mutation in melanoma occurs in NRAS oncogene, being a more aggressive disease that has no effective approved treatment. Besides, cellular plasticity limits better outcomes of the advanced and therapy-resistant patients. Peroxiredoxins (PRDXs) control cellular processes through direct hydrogen peroxide oxidation or by redox-relaying processes. Here, we demonstrated that PRDX2 could act as a modulator of multiple EMT markers in NRAS-mutated melanomas. PRDX2 knockdown lead to phenotypic changes towards invasion in human reconstructed skin and the treatment with a PRDX mimetic (gliotoxin), decreased migration in PRDX2-deficient cells. We also confirmed the favorable clinical outcome of patients expressing PRDX2 in a large primary melanoma cohort. This study contributes to our knowledge about genes involved in phenotype switching and opens a new perspective for PRDX2 as a biomarker and target in NRAS-mutated melanomas.
Insights
Researchers found that PRDX2 influences aggressive traits in NRAS-mutated melanoma. Lower PRDX2 levels promote cancer spread, suggesting PRDX2 as a potential biomarker and therapeutic target for this challenging melanoma subtype.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- NRAS mutations are common in aggressive melanoma, often leading to therapy resistance and poor outcomes.
- Cellular plasticity contributes to the challenges in treating advanced and resistant melanoma.
- Peroxiredoxins (PRDXs) are key regulators of cellular processes via hydrogen peroxide oxidation and redox signaling.
Purpose of the Study:
- To investigate the role of PRDX2 in NRAS-mutated melanoma.
- To explore PRDX2 as a potential modulator of epithelial-mesenchymal transition (EMT) and cellular plasticity.
- To evaluate PRDX2 as a prognostic biomarker and therapeutic target in NRAS-mutated melanoma.
Main Methods:
- PRDX2 knockdown experiments in human reconstructed skin models.
- Treatment of PRDX2-deficient cells with a PRDX mimetic (gliotoxin).
- Analysis of PRDX2 expression in a large primary melanoma patient cohort.
Main Results:
- PRDX2 knockdown induced phenotypic changes associated with invasion in NRAS-mutated melanoma models.
- Gliotoxin treatment reduced migration in PRDX2-deficient melanoma cells.
- High PRDX2 expression correlated with favorable clinical outcomes in patients with primary melanoma.
Conclusions:
- PRDX2 acts as a modulator of EMT markers in NRAS-mutated melanomas.
- PRDX2 plays a role in regulating melanoma cell migration and invasion.
- PRDX2 presents a promising biomarker and therapeutic target for NRAS-mutated melanoma.
More Related Videos
11:32Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
07:41A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Related Concept Videos
MAPK Signaling Cascades
Mitogens and the Cell Cycle
Abnormal Proliferation
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
The Intrinsic Apoptotic Pathway
The Ras Gene
Ras is a...