Matches in SemOpenAlex for { <https://semopenalex.org/work/W4296564552> ?p ?o ?g. }
- W4296564552 abstract "Therapy with radiation plus cisplatin kills HPV+ oropharyngeal squamous cell carcinomas (OPSCCs) by increasing reactive oxygen species beyond cellular antioxidant capacity. To explore why these standard treatments fail for some patients, we evaluated whether the variation in HPV oncoprotein levels among HPV+ OPSCCs affects mitochondrial metabolism, a source of antioxidant capacity. In cell line and patient-derived xenograft models, levels of HPV full-length E6 (fl-E6) inversely correlated with oxidative phosphorylation, antioxidant capacity, and therapy resistance, and fl-E6 was the only HPV oncoprotein to display such correlations. Ectopically expressing fl-E6 in models with low baseline levels reduced mitochondrial mass, depleted antioxidant capacity, and sensitized to therapy. In this setting, fl-E6 repressed the peroxisome proliferator-activated receptor gamma co-activator 1α/estrogen-related receptor α (PGC-1α/ERRα) pathway for mitochondrial biogenesis by reducing p53-dependent PGC-1α transcription. Concordant observations were made in 3 clinical cohorts, where expression of mitochondrial components was higher in tumors of patients with reduced survival. These tumors contained the lowest fl-E6 levels, the highest p53 target gene expression, and an activated PGC-1α/ERRα pathway. Our findings demonstrate that E6 can potentiate treatment responses by depleting mitochondrial antioxidant capacity and provide evidence for low E6 negatively affecting patient survival. E6's interaction with the PGC-1α/ERRα axis has implications for predicting and targeting treatment resistance in OPSCC." @default.
- W4296564552 created "2022-09-21" @default.
- W4296564552 creator A5004485035 @default.
- W4296564552 creator A5006164640 @default.
- W4296564552 creator A5012701649 @default.
- W4296564552 creator A5013962604 @default.
- W4296564552 creator A5023412463 @default.
- W4296564552 creator A5028299159 @default.
- W4296564552 creator A5033883424 @default.
- W4296564552 creator A5048903694 @default.
- W4296564552 creator A5049240982 @default.
- W4296564552 creator A5052023689 @default.
- W4296564552 creator A5065954539 @default.
- W4296564552 creator A5076660694 @default.
- W4296564552 creator A5088400169 @default.
- W4296564552 creator A5089664025 @default.
- W4296564552 creator A5090270861 @default.
- W4296564552 date "2022-09-22" @default.
- W4296564552 modified "2023-09-29" @default.
- W4296564552 title "HPV E6 regulates therapy responses in oropharyngeal cancer by repressing the PGC-1α/ERRα axis" @default.
- W4296564552 cites W1782055207 @default.
- W4296564552 cites W1831319429 @default.
- W4296564552 cites W1860866234 @default.
- W4296564552 cites W1868543250 @default.
- W4296564552 cites W1966458894 @default.
- W4296564552 cites W1969392895 @default.
- W4296564552 cites W1972256398 @default.
- W4296564552 cites W1972618720 @default.
- W4296564552 cites W1987702513 @default.
- W4296564552 cites W2000065704 @default.
- W4296564552 cites W2020954198 @default.
- W4296564552 cites W2026084994 @default.
- W4296564552 cites W2031757213 @default.
- W4296564552 cites W2035302428 @default.
- W4296564552 cites W2036199480 @default.
- W4296564552 cites W2046566365 @default.
- W4296564552 cites W2053249188 @default.
- W4296564552 cites W2077645437 @default.
- W4296564552 cites W2108564369 @default.
- W4296564552 cites W2110664940 @default.
- W4296564552 cites W2111442242 @default.
- W4296564552 cites W2124098526 @default.
- W4296564552 cites W2127659234 @default.
- W4296564552 cites W2128284013 @default.
- W4296564552 cites W2128962855 @default.
- W4296564552 cites W2130030488 @default.
- W4296564552 cites W2135994263 @default.
- W4296564552 cites W2139601917 @default.
- W4296564552 cites W2144542772 @default.
- W4296564552 cites W2151269016 @default.
- W4296564552 cites W2164277862 @default.
- W4296564552 cites W2214074259 @default.
- W4296564552 cites W2231633301 @default.
- W4296564552 cites W2345692510 @default.
- W4296564552 cites W2401291964 @default.
- W4296564552 cites W2480725775 @default.
- W4296564552 cites W2527908102 @default.
- W4296564552 cites W2528985990 @default.
- W4296564552 cites W2586267950 @default.
- W4296564552 cites W2591662415 @default.
- W4296564552 cites W2739132338 @default.
- W4296564552 cites W2761312364 @default.
- W4296564552 cites W2771559600 @default.
- W4296564552 cites W2788842984 @default.
- W4296564552 cites W2792033579 @default.
- W4296564552 cites W2894630945 @default.
- W4296564552 cites W2901263658 @default.
- W4296564552 cites W2901385432 @default.
- W4296564552 cites W2910156730 @default.
- W4296564552 cites W2975077252 @default.
- W4296564552 cites W3000042774 @default.
- W4296564552 cites W3005689864 @default.
- W4296564552 cites W3006316914 @default.
- W4296564552 cites W3032066929 @default.
- W4296564552 cites W3043817571 @default.
- W4296564552 cites W3080640400 @default.
- W4296564552 cites W3092645651 @default.
- W4296564552 cites W3093151636 @default.
- W4296564552 cites W3210363199 @default.
- W4296564552 cites W4221135882 @default.
- W4296564552 cites W4225992009 @default.
- W4296564552 cites W4235433825 @default.
- W4296564552 doi "https://doi.org/10.1172/jci.insight.159600" @default.
- W4296564552 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36134662" @default.
- W4296564552 hasPublicationYear "2022" @default.
- W4296564552 type Work @default.
- W4296564552 citedByCount "3" @default.
- W4296564552 countsByYear W42965645522023 @default.
- W4296564552 crossrefType "journal-article" @default.
- W4296564552 hasAuthorship W4296564552A5004485035 @default.
- W4296564552 hasAuthorship W4296564552A5006164640 @default.
- W4296564552 hasAuthorship W4296564552A5012701649 @default.
- W4296564552 hasAuthorship W4296564552A5013962604 @default.
- W4296564552 hasAuthorship W4296564552A5023412463 @default.
- W4296564552 hasAuthorship W4296564552A5028299159 @default.
- W4296564552 hasAuthorship W4296564552A5033883424 @default.
- W4296564552 hasAuthorship W4296564552A5048903694 @default.
- W4296564552 hasAuthorship W4296564552A5049240982 @default.
- W4296564552 hasAuthorship W4296564552A5052023689 @default.
- W4296564552 hasAuthorship W4296564552A5065954539 @default.