ArticleFree radical biology & medicine2012
Nox4 involvement in TGF-beta and SMAD3-driven induction of the epithelial-to-mesenchymal transition and migration of breast epithelial cells.
Article in Free radical biology & medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 1 of them a synthesis that pooled it.
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Who cites it
121 citing papers in PubMed, 1 synthesis or guideline pooled it, 198 citations in OpenAlex.
- Potential Therapeutic Effects of Natural Plant Compounds in Kidney Disease.Molecules (Basel, Switzerland) · 2021Pooled it
- A Systems View of Posterior Capsule Opacification: TGF-β/ROS Signaling, Mitochondrial Homeostasis, and Injury/Aging Cues-Therapeutic Opportunities.Investigative ophthalmology & visual science · 2026Review
- Circulating Thioredoxin 1 as an Adjunct to Mammography for Breast Cancer Detection: A Multicenter Clinical Validation Study.Cancers · 2026Article
- EndMT in vascular cognitive impairment and dementia: mechanisms, evidence gaps, and therapeutic opportunities.Molecular medicine (Cambridge, Mass.) · 2026Review
- The Pro-Metastatic Roles of ROS.Antioxidants (Basel, Switzerland) · 2026Review
- From a Shared Stress to Cell-Type-Specific Responses: The Heterogeneous Mechanisms of High Glucose-Induced Cellular Senescence in Diabetic Kidney Disease.Journal of diabetes research · 2026Review
- Nicotinamide adenine dinucleotide phosphate oxidase 4 in lung disease: a review of its biology and therapeutic potential.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- Wuweizisu B for cancer treatment from multitarget mechanisms to precision delivery strategies (Review).International journal of molecular medicine · 2025Review
- Transforming corneal alkali burn treatment: unveiling mechanisms and pioneering therapies from bench to bedside.Journal of translational medicine · 2025Review
- Long-term dynamic profiles of cognitive kinases induced by different learning protocols.bioRxiv : the preprint server for biology · 2025Article
- Reduced glutathione enhances adipose tissue-derived mesenchymal stem cell engraftment efficiency for liver fibrosis by targeting TGFβ1/SMAD3/NOX4 pathway.Bioengineering & translational medicine · 2025Article
- Gene Expression and Prognostic Value of NADPH Oxidase Enzymes in Breast Cancer.International journal of molecular sciences · 2024Article
- Metformin Attenuates TGF-β1-Induced Fibrosis in Salivary Gland: A Preliminary Study.International journal of molecular sciences · 2023Article
- Multifaceted role of redox pattern in the tumor immune microenvironment regarding autophagy and apoptosis.Molecular cancer · 2023Review
- Screening of key genes related to ferroptosis and a molecular interaction network analysis in colorectal cancer using machine learning and bioinformatics.Journal of gastrointestinal oncology · 2023Article
- Role of NADPH Oxidase 4 in Corneal Endothelial Cells Is Mediated by Endoplasmic Reticulum Stress and Autophagy.Antioxidants (Basel, Switzerland) · 2023Article
- Mutant p53 and NOX4 are modulators of a CCL5-driven pro-migratory secretome.Free radical biology & medicine · 2023Article
- Functional interactions between NADPH oxidase 5 and actin.Frontiers in cell and developmental biology · 2023Article
- Particulate matter promotes the epithelial to mesenchymal transition in human lung epithelial cells via the ROS pathway.American journal of translational research · 2023Article
- NOX4-derived ROS Regulates Aerobic Glycolysis of Breast Cancer through YAP Pathway.Journal of Cancer · 2023Article
61 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The epithelial-to-mesenchymal transition (EMT) is the development of increased cell plasticity that occurs normally during wound healing and embryonic development and can be coopted for cancer invasion and metastasis. TGF-beta induces EMT but the mechanism is unclear. Our studies suggest that Nox4, a member of the NADPH oxidase (Nox) family, is a source of reactive oxygen species (ROS) affecting cell migration and fibronectin expression, an EMT marker, in normal and metastatic breast epithelial cells. We found that TGF-beta induces Nox4 expression (mRNA and protein) and ROS generation in normal (MCF10A) and metastatic (MDA-MB-231) human breast epithelial cells. Conversely, cells expressing a dominant-negative form of Nox4 or Nox4-targeted shRNA showed significantly lower ROS production on TGF-beta treatment. Expression of a constitutively active TGF-beta receptor type I significantly increased Nox4 promoter activity, mRNA and protein expression, and ROS generation. Nox4 transcriptional regulation by TGF-beta was SMAD3 dependent based on the effect of constitutively active SMAD3 increasing Nox4 promoter activity, whereas dominant-negative SMAD3 or SIS3, a SMAD3-specific inhibitor, had the opposite effect. Furthermore, Nox4 knockdown, dominant-negative Nox4 or SMAD3, or SIS3 blunted TGF-beta induced wound healing and cell migration, whereas cell proliferation was not affected. Our experiments further indicate that Nox4 plays a role in TGF-beta regulation of fibronectin mRNA expression, based on the effects of dominant-negative Nox4 in reducing fibronectin mRNA in TGF-beta-treated MDA-MB-231and MCF10A cells. Collectively, these data indicate that Nox4 contributes to NADPH oxidase-dependent ROS production that may be critical for the progression of the EMT in breast epithelial cells, and thereby has therapeutic implications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.