{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Garcia-Gomez P"],"funding":["O. E. och Edla Johanssons Vetenskapliga Stiftelse","Svenska Läkaresällskapet","Stiftelsen Lars Hiertas Minne","Magnus Bergvalls Stiftelse","Petrus och Augusta Hedlunds Stiftelse","Ludwig Institute for Cancer Research","Cancerfonden"],"pagination":["1891-1912"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9067149"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(9)"],"pubmed_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."],"journal":["Molecular oncology"],"pubmed_title":["NOX4 regulates TGFβ-induced proliferation and self-renewal in glioblastoma stem cells."],"pmcid":["PMC9067149"],"funding_grant_id":["M2019‐1065","M2020‐1274","2019‐03444","FO2020‐0335","CAN 2012/1186","2020‐03781","SLS‐887701","CAN 2017/1066"],"pubmed_authors":["Tzavlaki K","Carreras-Puigvert J","S Dadras M","Moren A","Bellomo C","Golan I","Garcia-Gomez P","Mezheyeuski A","Caja L"],"additional_accession":[]},"is_claimable":false,"name":"NOX4 regulates TGFβ-induced proliferation and self-renewal in glioblastoma stem cells.","description":"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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 May","modification":"2025-04-19T12:55:09.429Z","creation":"2025-04-19T12:55:09.429Z"},"accession":"S-EPMC9067149","cross_references":{"pubmed":["35203105"],"doi":["10.1002/1878-0261.13200"]}}