Matches in SemOpenAlex for { <https://semopenalex.org/work/W2403046739> ?p ?o ?g. }
- W2403046739 abstract "Cutaneous squamous cell carcinomas (cSCC) are the most common and highly mutated human malignancies, challenging identification of driver mutations and targeted therapies. Transcription factor NF-E2 p45-related factor 2 (Nrf2) orchestrates a cytoprotective inducible program, which counteracts the damaging effects of solar UV radiation, the main etiological factor in cSCC development. Downregulation of Kelch-like ECH-associated protein 1 (Keap1), a Cullin-3/Rbx1 ubiquitin ligase substrate adaptor protein, which mediates the ubiquitination and proteasomal degradation of Nrf2, has a strong protective effect in a preclinical model of cSCC. However, in addition to Nrf2, Keap1 affects ubiquitination of other proteins in the carcinogenesis process, including proteins involved in inflammation and DNA damage repair. Here, we generated Keap1(flox/flox) SKH-1 hairless mice in which Nrf2 is disrupted (Keap1(flox/flox)/Nrf2(-/-)) and subjected them chronically to solar-simulated UV radiation. We found that the incidence, multiplicity and burden of cSCC that form in Keap1(flox/flox)/Nrf2(-/-) mice are much greater than in their Keap1(flox/flox)/Nrf2(+/+) counterparts, establishing Nrf2 activation as the protection mediator. Our findings further imply that inhibition of Nrf2 globally, a strategy proposed for cancer treatment, is unlikely to be beneficial." @default.
- W2403046739 created "2016-06-24" @default.
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- W2403046739 date "2016-05-24" @default.
- W2403046739 modified "2023-10-11" @default.
- W2403046739 title "Loss of Nrf2 abrogates the protective effect of Keap1 downregulation in a preclinical model of cutaneous squamous cell carcinoma" @default.
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- W2403046739 doi "https://doi.org/10.1038/srep25804" @default.
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