ArticleJCI insight2022
HPV E6 regulates therapy responses in oropharyngeal cancer by repressing the PGC-1α/ERRα axis.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- The rs17782313 polymorphism near MC4R gene confers a high risk of obesity and hyperglycemia, while PGC1α rs8192678 polymorphism is weakly correlated with glucometabolic disorder: a systematic review and meta-analysis.Frontiers in endocrinology · 2023Pooled it
- Targeting metabolic reprogramming in HPV-associated oral squamous cell carcinoma: current advances, challenges, and clinical prospects.Journal of molecular histology · 2026Review
- Therapeutic scheduling of WEE1 inhibition preserves T cell function and promotes immune control of HPVbioRxiv : the preprint server for biology · 2026Article
- The pivotal role of mitochondria in osteoporosis: From pathogenesis to future therapies.Biochemistry and biophysics reports · 2026Review
- BVDV utilizes PGC-1α downregulation to remodel the mitochondrial metabolic microenvironment, enhancing viral replication and impairing host immunity.Frontiers in veterinary science · 2026Article
- Splicing of HPV16 E6 promotes aggressive invasion in oropharyngeal cancer via endocytosis of E-cadherin.bioRxiv : the preprint server for biology · 2025Article
- Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025Review
- Tumor-intrinsic and immune-related features associated with treatment failure in human papillomavirus-related oropharyngeal cancer.Journal of the National Cancer Institute · 2025Article
- Nanoparticle-mediated targeting of PGC-1α reveals critical metabolic pathways in bladder cancer metastasis.Communications biology · 2025Article
- Review
- Association of oropharyngeal cancer recurrence with tumor-intrinsic and immune-mediated sequelae of reduced genomic instability.bioRxiv : the preprint server for biology · 2024Article
- Fibroblast stromal support model for predicting human papillomavirus-associated cancer drug responses.Journal of virology · 2024Article
- Analysis of Expression and Regulation of AKR1C2 in HPV-Positive and -Negative Oropharyngeal Squamous Cell Carcinoma.Cancers · 2024Article
- Dynamics of oral human papillomavirus infection in healthy population and head and neck cancer.Cancer medicine · 2023Review
- Hepatitis B virus infection: An insight into the clinical connection and molecular interaction between hepatitis B virus and host extrahepatic cancer risk.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.