Interplay between Nrf2 and ROS in regulating epithelial-mesenchymal transition: implications for cancer metastasis and therapy.

Xu Y, Hu S, Chen R, Xu S, Yu G, Ji L

Molecular biology reports [Mol Biol Rep] 2025 Jun 23; Vol. 52 (1), pp. 628. Date of Electronic Publication: 2025 Jun 23.

2025

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Title

Interplay between Nrf2 and ROS in regulating epithelial-mesenchymal transition: implications for cancer metastasis and therapy.

Authors

Xu Y, Hu S, Chen R, Xu S, Yu G, Ji L

Source

Molecular biology reports [Mol Biol Rep] 2025 Jun 23; Vol. 52 (1), pp. 628. Date of Electronic Publication: 2025 Jun 23.

Abstract

Competing Interests: Declarations. Ethical approval: Not applicable. Competing interests: The authors declare no competing interests.
Epithelial-mesenchymal transition (EMT), including developmental (Type I), wound healing (Type II), and pathological (Type III) subtypes, constitutes a critical driver of cancer metastasis. This review analyzes the redox interplay between nuclear factor erythroid 2-related factor 2 (Nrf2) and reactive oxygen species (ROS) in EMT regulation and cancer progression. Nrf2 maintains redox homeostasis through antioxidant gene activation while paradoxically promoting tumor survival and drug resistance via Keap1-dependent degradation and phosphorylation-mediated stabilization. ROS generated through mitochondrial and NADPH oxidase pathways exhibit dual functionality: moderate levels activate EMT transcription factors to drive metastasis and cancer stem cells (CSCs) plasticity, whereas excessive ROS induce apoptosis and ferroptosis. While Nrf2 typically suppresses EMT through ROS neutralization and epithelial integrity preservation, chronic Nrf2 activation in CSCs paradoxically sustains metastatic potential through redox buffering. This synthesis delineates the spatiotemporal regulation of Nrf2-ROS-EMT networks across tumor microenvironments, emphasizing therapeutic opportunities through redox balance modulation and pathway-specific Nrf2 inhibition in advanced malignancies.
(© 2025. The Author(s).)

Language

English

Journal Info

Publisher: Reidel Country of Publication: Netherlands NLM ID: 0403234 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-4978 (Electronic) Linking ISSN: 03014851 NLM ISO Abbreviation: Mol Biol Rep Subsets: MEDLINE

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Update Code

20250624

Database	MEDLINE
Publication Type	Journal Article; Review
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Contributed Indexing	Keywords: Cancer stem cells; Epithelial-mesenchymal transition (EMT); Nrf2; Oxidative stress; ROS
DOI	10.1007/s11033-025-10731-9
PMID	40549063

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