biostudies-literatureHelfinger VBritish Heart FoundationDeutsche ForschungsgemeinschaftFraunhofer GesellschaftBiotechnology and Biological Sciences Research Councile2020152118https://www.ebi.ac.uk/biostudies/studies/S-EPMC7980388biostudies-literatureUnknown118(11)Reactive oxygen species (ROS) can cause cellular damage and promote cancer development. Besides such harmful consequences of overproduction of ROS, all cells utilize ROS for signaling purposes and stabilization of cell homeostasis. In particular, the latter is supported by the NADPH oxidase 4 (Nox4) that constitutively produces low amounts of H₂O₂ By that mechanism, Nox4 forces differentiation of cells and prevents inflammation. We hypothesize a constitutive low level of H₂O₂ maintains basal activity of cellular surveillance systems and is unlikely to be cancerogenic. Utilizing two different murine models of cancerogen-induced solid tumors, we found that deletion of Nox4 promotes tumor formation and lowers recognition of DNA damage. Nox4 supportsProceedings of the National Academy of Sciences of the United States of AmericaGenetic deletion of Nox4 enhances cancerogen-induced formation of solid tumors.PMC7980388SFB815/Z1SCHR1241/1-1TRIPSFB815/TP8CH/1999001/11735SFB815/TP1BBS/E/B/000C0415Heidler JHenke NWittig IRezende FSchroder KFreiherr von Gall FRadeke HHHelfinger VAnderson KFulda SShah AMMarschall VSchmid TBrune BBrandes RPKunze MMfalseGenetic deletion of Nox4 enhances cancerogen-induced formation of solid tumors.Reactive oxygen species (ROS) can cause cellular damage and promote cancer development. Besides such harmful consequences of overproduction of ROS, all cells utilize ROS for signaling purposes and stabilization of cell homeostasis. In particular, the latter is supported by the NADPH oxidase 4 (Nox4) that constitutively produces low amounts of H₂O₂ By that mechanism, Nox4 forces differentiation of cells and prevents inflammation. We hypothesize a constitutive low level of H₂O₂ maintains basal activity of cellular surveillance systems and is unlikely to be cancerogenic. Utilizing two different murine models of cancerogen-induced solid tumors, we found that deletion of Nox4 promotes tumor formation and lowers recognition of DNA damage. Nox4 supports2021-01-01T00:00:00Z2021 Mar2026-05-02T13:45:00.042Z2022-02-09T14:44:49.52ZS-EPMC79803883383659010.1073/pnas.2020152118