ArticleCancer prevention research (Philadelphia, Pa.)2012
Inhibition of mTOR suppresses UVB-induced keratinocyte proliferation and survival.
Article in Cancer prevention research (Philadelphia, Pa.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Sirolimus for Secondary Prevention of Cutaneous Squamous Cell Carcinoma in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.International journal of dermatology · 2026Pooled it
- Activation of the PI3K/Akt/mTOR and MAPK Signaling Pathways in Response to Acute Solar-Simulated Light Exposure of Human Skin.Cancer prevention research (Philadelphia, Pa.) · 2015Trial
- Alpha-Ketoglutarate Attenuates UVB-Induced Skin Photoaging by Restoring Mitochondrial Redox Homeostasis.Antioxidants (Basel, Switzerland) · 2026Article
- Article
- Atorvastatin calcium alleviates UVB-induced HaCat cell senescence and skin photoaging.Scientific reports · 2024Article
- β-endorphin suppresses ultraviolet B irradiation-induced epidermal barrier damage by regulating inflammation-dependent mTORC1 signaling.Scientific reports · 2023Article
- Cholesterol biosynthesis defines oligodendrocyte precursor heterogeneity between brain and spinal cord.Cell reports · 2022Article
- Autophagy-related Proteins in Genome Stability: Autophagy-Dependent and Independent Actions.International journal of biological sciences · 2022Review
- Article
- Nicotinamide Mononucleotide Combined WithFrontiers in pharmacology · 2021Article
- The Protective Effects of a Combination of an Arginine Silicate Complex and Magnesium Biotinate Against UV-Induced Skin Damage in Rats.Frontiers in pharmacology · 2021Article
- Article
- Effects of the mTOR and AKT genes polymorphisms on systemic lupus erythematosus risk.Molecular biology reports · 2020Article
- Mechanistic Target of Rapamycin Regulates the Oligodendrocyte Cytoskeleton during Myelination.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Piceatannol Inhibits P. acnes-Induced Keratinocyte Proliferation and Migration by Downregulating Oxidative Stress and the Inflammatory Response.Inflammation · 2020Article
- Fibroblast growth factor receptor promotes progression of cutaneous squamous cell carcinoma.Molecular carcinogenesis · 2019Article
- Inhibition of mTORC2 enhances UVB-induced apoptosis in keratinocytes through a mechanism dependent on the FOXO3a transcriptional target NOXA but independent of TRAIL.Cellular signalling · 2018Article
- Knockout of Raptor destabilizes ornithine decarboxylase mRNA and decreases binding of HuR to the ODC transcript in cells exposed to ultraviolet-B irradiation.Biochemical and biophysical research communications · 2018Article
- Protective role of integrin-linked kinase against oxidative stress and in maintenance of genomic integrity.Oncotarget · 2018Article
- Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
UV radiation is the major risk factor for developing skin cancer, the most prevalent cancer worldwide. Several studies indicate that mTOR signaling is activated by UVB and may play an important role in skin tumorigenesis. mTOR exists in two functionally and compositionally distinct protein complexes: the rapamycin-sensitive mTOR complex 1 (mTORC1) and the rapamycin-resistant mTOR complex 2 (mTORC2). The purpose of these studies was to investigate the roles of the two mTOR complexes in UVB-mediated proliferation and apoptosis in the skin. We used rapamycin, a pharmacologic inhibitor of mTORC1, and an inducible mTOR-deficient (K5-CreER(T2);mTOR(fl/fl)) mouse model that allows epidermal-specific disruption of mTOR following topical treatment with 4-hydroxytamoxifen (4OHT). Rapamycin blocked UVB-induced phosphorylation of S6K, the downstream target of mTORC1, and significantly reduced UVB-stimulated epidermal proliferation and cell-cycle progression, but had no effect on cell death. In contrast, mTOR deletion, which attenuated UVB-induced phosphorylation of both S6K and the mTORC2 target AKT(Ser473), significantly increased apoptosis both in vivo and in keratinocyte cultures, in addition to reducing hyperproliferation following UVB irradiation. The role of mTORC2 in UVB-induced prosurvival signaling was verified in Rictor(-/-) mouse embryo fibroblasts, which lack functional mTORC2 and were more sensitive to UVB-induced apoptosis than controls. These studies show that mTORC1 and mTORC2 play unique but complementary roles in controlling proliferation and apoptosis in the skin. Our findings underscore the importance of both mTOR complexes in mediating UVB-induced signaling in keratinocytes and provide new insight into the pathogenesis of skin cancer.
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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.