ArticleMolecular oncology2022
NOX4 regulates TGFβ-induced proliferation and self-renewal in glioblastoma stem cells.
Article in Molecular oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 36 citations in OpenAlex.
- Redox Regulation in Glioblastoma: Mechanisms, Biomarkers, and Therapeutic Implications.International journal of molecular sciences · 2026Review
- RAB4A acts as a negative feedback regulator of extracellular vesicle secretion during TGF-β signaling.The FEBS journal · 2026Article
- The Interplay Between Periodontitis and Atrial Fibrillation: Inflammation as a Common Pathophysiological Bridge.International journal of molecular sciences · 2026Review
- Targeting dormant cancer cells: ferroptosis as a precision therapeutic strategy.Cellular & molecular biology letters · 2026Review
- Review
- Immune factors and their role in tumor aggressiveness in glioblastoma: Atypical cadherin FAT1 as a promising target for combating immune evasion.Cellular & molecular biology letters · 2025Review
- NOX4 serves as a pan-cancer prognostic biomarker and therapeutic target in tumorigenesis.Scientific reports · 2025Article
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Targeting cancer stem cells by TPA leads to inhibition of refractory sarcoma and extended overall survival.Molecular therapy. Oncology · 2024Article
- TGFβ family signaling in human stem cell self-renewal and differentiation.Cell regeneration (London, England) · 2024Review
- Review
- Nrf2/Keap1/ARE regulation by plant secondary metabolites: a new horizon in brain tumor management.Cell communication and signaling : CCS · 2024Review
- Balanced Duality: HInternational journal of molecular sciences · 2024Review
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Glioma Stem Cells-Features for New Therapy Design.Cancers · 2024Review
- Identification of potential biomarkers for aging diagnosis of mesenchymal stem cells derived from the aged donors.Stem cell research & therapy · 2024Article
- Nrf2-mediated redox balance alleviates LPS-induced vascular endothelial cell inflammation by inhibiting endothelial cell ferroptosis.Scientific reports · 2024Article
- The TGF-β Family in Glioblastoma.International journal of molecular sciences · 2024Review
- Targeting ROS production through inhibition of NADPH oxidases.Nature chemical biology · 2023Article
- The long non-coding RNA LINC00707 interacts with Smad proteins to regulate TGFβ signaling and cancer cell invasion.Cell communication and signaling : CCS · 2023Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma (GBM) is the most aggressive and common glioma subtype, with a median survival of 15 months after diagnosis. Current treatments have limited therapeutic efficacy; thus, more effective approaches are needed. The glioblastoma tumoural mass is characterised by a small cellular subpopulation - glioblastoma stem cells (GSCs) - that has been held responsible for glioblastoma initiation, cell invasion, proliferation, relapse and resistance to chemo- and radiotherapy. Targeted therapies against GSCs are crucial, as is understanding the molecular mechanisms that govern the GSCs. Transforming growth factor β (TGFβ) signalling and reactive oxygen species (ROS) production are known to govern and regulate cancer stem cell biology. Among the differentially expressed genes regulated by TGFβ in a transcriptomic analysis of two different patient-derived GSCs, we found NADPH oxidase 4 (NOX4) as one of the top upregulated genes. Interestingly, when patient tissues were analysed, NOX4 expression was found to be higher in GSCs versus differentiated cells. A functional analysis of the role of NOX4 downstream of TGFβ in several patient-derived GSCs showed that TGFβ does indeed induce NOX4 expression and increases ROS production in a NOX4-dependent manner. NOX4 downstream of TGFβ regulates GSC proliferation, and NOX4 expression is necessary for TGFβ-induced expression of stem cell markers and of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2), which in turn controls the cell's antioxidant and metabolic responses. Interestingly, overexpression of NOX4 recapitulates the effects induced by TGFβ in GSCs: enhanced proliferation, stemness and NRF2 expression. In conclusion, this work functionally establishes NOX4 as a key mediator of GSC biology.
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