ArticleHistology and histopathology2025
NRF3 suppresses the metastasis of triple-negative breast cancer cells by inhibiting ERK activation in a ROS-dependent manner.
Article in Histology and histopathology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Integrating single-cell RNA and bulk RNA sequencing data to identify prognostic genes associated with pyrimidine metabolism in triple-negative breast cancer by machine learning algorithm combinations.Discover oncology · 2026Article
- Nrf3: an emerging player in cancer, inflammation, and cellular homeostasis.Molecular biology reports · 2026Review
- Targeting Nrf3-Pitx2-ROS axis represents a promising therapeutic strategy for myocardial infarction.MedScience · 2026Article
- The Anti-lung Cancer Mechanism of Qingzao Jiufei Decoction was Studied based on Network Pharmacology, Molecular Docking, and Experimental Verification.Combinatorial chemistry & high throughput screening · 2026Article
- Interactions between LncRNAs and MAPK signaling pathways in the pathogenesis of breast cancer.Cancer cell international · 2025Review
- NRF3 suppresses the malignant progression of TNBC by promoting M1 polarization of macrophages via ROS/HMGB1 axis.Cancer biology & therapy · 2024Article
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Authors and funding
6 authors.
Funding
Abstract
purposeOur previous study demonstrated that NRF3 (NFE2L3, Nuclear Factor-erythroid 2-related factor 3) could suppress cell metastasis and proliferation in breast cancer. In this study, we investigated the mechanisms underlying its function in breast cancer.
methodsIn the present study, NRF3 expression and its clinical characteristics in breast cancer were analyzed using public datasets and clinical specimens. After breast cancer cells were overexpressed NRF3, FACS was used to detect the intracellular ROS levels. The migration and invasion activities of NRF3-ectopic expressed breast cancer cells were determined by transwell assay. To validate the role of ROS/ERK axis in the inhibitory effect of NRF3 in cell metastasis, ROS scavenger NAC was also included.
resultsWe found that NRF3 mRNA was highly expressed, while NRF3 protein was extremely lowly expressed in breast cancer tissues compared with their normal counterparts, and low level NRF3 was associated with poorer prognosis in patients with triple negative breast cancer (TNBC). More interestingly, overexpression of NRF3 protein significantly increased cellular ROS production and dramatically decreased p-ERK level and cell migration in TNBC cells. Mechanistically, NRF3 protein was found to be mutually regulated by valosin-containing protein (VCP). Strikingly, VCP-knockdown dramatically increased NRF3 protein expression, but NRF3-knockin also decreased VCP expression in return. Moreover, antioxidant NAC treatment effectively increased the level of p-ERK and VCP expression, as well as cell migration and invasion abilities of TNBC cells.
conclusionNRF3, a tumor suppressor downregulated by VCP, could attenuate cell metastasis in TNBC cells by increasing cellular ROS accumulation and subsequently inhibiting the ERK phosphorylation.
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