ArticleProceedings of the National Academy of Sciences of the United States of America2011
Protection from UV-induced skin carcinogenesis by genetic inhibition of the ataxia telangiectasia and Rad3-related (ATR) kinase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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
31 citing papers in PubMed, 56 citations in OpenAlex.
- Review
- Article
- Phototherapy and DNA Damage: A Systematic Review.The Journal of clinical and aesthetic dermatology · 2023Article
- The Aryl Hydrocarbon Receptor in the Pathogenesis of Environmentally-Induced Squamous Cell Carcinomas of the Skin.Frontiers in oncology · 2022Review
- The 6-4 photoproduct is the trigger of UV-induced replication blockage and ATR activation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Deciphering UV-induced DNA Damage Responses to Prevent and Treat Skin Cancer.Photochemistry and photobiology · 2020Review
- Green Composite of Instant Coffee and Poly(vinyl alcohol): An Excellent Transparent UV-Shielding Material with Superior Thermal-Oxidative Stability.Industrial & engineering chemistry research · 2020Article
- Another Reason for Using Caffeine in Dermocosmetics: Sunscreen Adjuvant.Frontiers in physiology · 2019Article
- Targeting ATR in cancer.Nature reviews. Cancer · 2018Review
- Caffeine Protects Skin from Oxidative Stress-Induced Senescence through the Activation of Autophagy.Theranostics · 2018Article
- Biomedical Research as a Team Sport.The Journal of investigative dermatology · 2017Article
- Impact of Age and Insulin-Like Growth Factor-1 on DNA Damage Responses in UV-Irradiated Human Skin.Molecules (Basel, Switzerland) · 2017Review
- Molecular signaling cascades involved in nonmelanoma skin carcinogenesis.The Biochemical journal · 2016Review
- A neomorphic cancer cell-specific role of MAGE-A4 in trans-lesion synthesis.Nature communications · 2016Article
- ATR Kinase Inhibition Protects Non-cycling Cells from the Lethal Effects of DNA Damage and Transcription Stress.The Journal of biological chemistry · 2016Article
- Article
- Molecular Pathways: Targeting ATR in Cancer Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Review
- ATR Plays a Direct Antiapoptotic Role at Mitochondria, which Is Regulated by Prolyl Isomerase Pin1.Molecular cell · 2015Article
- A novel topical targeting system of caffeine microemulsion for inhibiting UVB-induced skin tumor: characterization, optimization, and evaluation.AAPS PharmSciTech · 2015Article
- Replication stress and cancer.Nature reviews. Cancer · 2015Review
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
Multiple human epidemiologic studies link caffeinated (but not decaffeinated) beverage intake with significant decreases in several types of cancer, including highly prevalent UV-associated skin carcinomas. The mechanism by which caffeine protects against skin cancer is unknown. Ataxia telangiectasia and Rad3-related (ATR) is a replication checkpoint kinase activated by DNA stresses and is one of several targets of caffeine. Suppression of ATR, or its downstream target checkpoint kinase 1 (Chk1), selectively sensitizes DNA-damaged and malignant cells to apoptosis. Agents that target this pathway are currently in clinical trials. Conversely, inhibition of other DNA damage response pathways, such as ataxia telangiectasia mutated (ATM) and BRCA1, promotes cancer. To determine the effect of replication checkpoint inhibition on carcinogenesis, we generated transgenic mice with diminished ATR function in skin and crossed them into a UV-sensitive background, Xpc(-/-). Unlike caffeine, this genetic approach was selective and had no effect on ATM activation. These transgenic mice were viable and showed no histological abnormalities in skin. Primary keratinocytes from these mice had diminished UV-induced Chk1 phosphorylation and twofold augmentation of apoptosis after UV exposure (P = 0.006). With chronic UV treatment, transgenic mice remained tumor-free for significantly longer (P = 0.003) and had 69% fewer tumors at the end of observation of the full cohort (P = 0.019), compared with littermate controls with the same genetic background. This study suggests that inhibition of replication checkpoint function can suppress skin carcinogenesis and supports ATR inhibition as the relevant mechanism for the protective effect of caffeinated beverage intake in human epidemiologic studies.
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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.