ArticleOncotarget2016
PI3K-PTEN dysregulation leads to mTOR-driven upregulation of the core clock gene BMAL1 in normal and malignant epithelial cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 55 citations in OpenAlex.
- Sensitivity Analysis of the Efficacy of Everolimus for Neurocognitive Symptoms in PTEN Hamartoma Tumor Syndrome.Advances in therapy · 2026Trial
- mTORC2-NaChannels (Austin, Tex.) · 2026Article
- Curcumin in High Doses Reverses the UV-B-InducedPharmaceuticals (Basel, Switzerland) · 2026Article
- Potential repurposing of lapatinib and pazopanib as neuroprotective agents in a rat model of Huntington's disease.Inflammopharmacology · 2025Article
- Latitudinal-environmental variations driving the local adaptation ofMarine life science & technology · 2025Article
- The Value of Punching It Out: Patient With Cowden Syndrome and MALT Lymphoma of the Lung.Case reports in oncological medicine · 2025Article
- The Common Hallmarks and Interconnected Pathways of Aging, Circadian Rhythms, and Cancer: Implications for Therapeutic Strategies.Research (Washington, D.C.) · 2025Review
- The rhythms of histones in regeneration: The epigenetic modifications determined by clock genes.Experimental dermatology · 2024Article
- The Relationship between Clock Genes, Sirtuin 1, and Mitochondrial Activity in Head and Neck Squamous Cell Cancer: Effects of Melatonin Treatment.International journal of molecular sciences · 2023Article
- Role of Melatonin in Cancer: Effect on Clock Genes.International journal of molecular sciences · 2023Review
- Major roles of the circadian clock in cancer.Cancer biology & medicine · 2023Review
- The role of microRNAs in the molecular link between circadian rhythm and autism spectrum disorder.Animal cells and systems · 2023Review
- Review
- From Tissue Physoxia to Cancer Hypoxia, Cost-Effective Methods to Study Tissue-Specific OInternational journal of molecular sciences · 2022Article
- A time to heal: microRNA and circadian dynamics in cutaneous wound repair.Clinical science (London, England : 1979) · 2022Review
- Article
- Clock at the Core of Cancer Development.Biology · 2021Review
- Review
- Precision Medicine Gains Momentum: Novel 3D Models and Stem Cell-Based Approaches in Head and Neck Cancer.Frontiers in cell and developmental biology · 2021Review
- Evaluation of Diagnostic Potential of Epigenetically Deregulated MiRNAs in Epithelial Ovarian Cancer.Frontiers in oncology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Dysfunctional clock signaling is observed in a variety of pathological conditions. Many members of the clock gene family are upregulated in tumor cells. Here, we explored the consequences of a commonly disrupted signaling pathway in head and neck cancer on the regulation of circadian clock genes. PTEN is a key molecular controller of the PI3K signaling, and loss of PTEN function is often observed in a variety of cancers. Our main goal was to determine whether PTEN regulates circadian clock signaling. We found that oxidation-driven loss of PTEN function resulted in the activation of mTOR signaling and activation of the core clock protein BMAL1 (also known as ARNTL). The PTEN-induced BMAL1 upregulation was further confirmed using small interference RNA targeting PTEN, and in vivo conditional depletion of PTEN from the epidermis. We observed that PTEN-driven accumulation of BMAL1 was mTOR-mediated and that administration of Rapamycin, a specific mTOR inhibitor, resulted in in vivo rescue of normal levels of BMAL1. Accumulation of BMAL1 by deletion of PER2, a Period family gene, was also rescued upon in vivo administration of mTOR inhibitor. Notably, BMAL1 regulation requires mTOR regulatory protein Raptor and Rictor. These findings indicate that mTORC1 and mTORC2 complex plays a critical role in controlling BMAL1, establishing a connection between PI3K signaling and the regulation of circadian rhythm, ultimately resulting in deregulated BMAL1 in tumor cells with disrupted PI3K signaling.
Indexed as
Identifiers
What OpenQuestion holds
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.