ArticleCell death & disease2017
Epidermal Rac1 regulates the DNA damage response and protects from UV-light-induced keratinocyte apoptosis and skin carcinogenesis.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Rac1 GTPase Regulates the SCFCancers · 2026Article
- Somatic mutations in IRE1α regulate keratinocyte migration and survival by differentially activating Rho GTPases.Journal of cell science · 2025Article
- Targeting dermatophyte Cdc42 and Rac GTPase signaling to hinder hyphal elongation and virulence.iScience · 2024Article
- A distinct pattern of growth and RAC1 signaling in melanoma brain metastasis cells.Neuro-oncology · 2023Article
- Influence of Inhibition of COX-2-Dependent Lipid Metabolism on Regulation of UVB-Induced Keratinocytes Apoptosis by Cannabinoids.Biomolecules · 2022Article
- UV-C Light-Based Surface Disinfection: Analysis of Its Virucidal Efficacy Using a Bacteriophage Model.International journal of environmental research and public health · 2022Article
- Analysis of bacterial contamination and the effectiveness of UV light-based reprocessing of everyday medical devices.PloS one · 2022Article
- UV light-based reprocessing of flexible endoscopes without working channel in Oto-Rhino-Laryngology: an effective method?European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2021Article
- Disease-Dependent Antiapoptotic Effects of Cannabidiol for Keratinocytes Observed upon UV Irradiation.International journal of molecular sciences · 2021Article
- Skin Cancers and the Contribution of Rho GTPase Signaling Networks to Their Progression.Cancers · 2021Review
- Inflammatory Molecules Associated with Ultraviolet Radiation-Mediated Skin Aging.International journal of molecular sciences · 2021Review
- A role for keratin 17 during DNA damage response and tumor initiation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- GEFT Inhibits Autophagy and Apoptosis in RhabdomyosarcomaFrontiers in oncology · 2021Article
- Differential Expression Profiles and Function Predictions for tRFs & tiRNAs in Skin Injury Induced by Ultraviolet Irradiation.Frontiers in cell and developmental biology · 2021Article
- m5C-Related Signatures for Predicting Prognosis in Cutaneous Melanoma with Machine Learning.Journal of oncology · 2021Article
- A Nobel-Winning Scientist: Aziz Sancar and the Impact of his Work on the Molecular Pathology of Neoplastic Diseases.Turk patoloji dergisi · 2021Review
- Keratinocyte Growth Factor 2 Ameliorates UVB-Induced Skin DamageFrontiers in pharmacology · 2021Article
- Mechanism underlying the effect of SO2-induced oxidation on human skin keratinocytes.Medicine · 2020Article
- UV light-based decontamination: an effective and fast way for disinfection of endoscopes in otorhinolaryngology?European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2020Article
- Induction of Autophagy by Baicalin Through the AMPK-mTOR Pathway Protects Human Skin Fibroblasts from Ultraviolet B Radiation-Induced Apoptosis.Drug design, development and therapy · 2020Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-melanoma skin cancer (NMSC) is the most common type of cancer. Increased expression and activity of Rac1, a small Rho GTPase, has been shown previously in NMSC and other human cancers; suggesting that Rac1 may function as an oncogene in skin. DMBA/TPA skin carcinogenesis studies in mice have shown that Rac1 is required for chemically induced skin papilloma formation. However, UVB radiation by the sun, which causes DNA damage, is the most relevant cause for NMSC. A potential role of Rac1 in UV-light-induced skin carcinogenesis has not been investigated so far. To investigate this, we irradiated mice with epidermal Rac1 deficiency (Rac1-EKO) and their controls using a well-established protocol for long-term UV-irradiation. Most of the Rac1-EKO mice developed severe skin erosions upon long-term UV-irradiation, unlike their controls. These skin erosions in Rac1-EKO mice healed subsequently. Surprisingly, we observed development of squamous cell carcinomas (SCCs) within the UV-irradiation fields. This shows that the presence of Rac1 in the epidermis protects from UV-light-induced skin carcinogenesis. Short-term UV-irradiation experiments revealed increased UV-light-induced apoptosis of Rac1-deficient epidermal keratinocytes in vitro as well as in vivo. Further investigations using cyclobutane pyrimidine dimer photolyase transgenic mice revealed that the observed increase in UV-light-induced keratinocyte apoptosis in Rac1-EKO mice is DNA damage dependent and correlates with caspase-8 activation. Furthermore, Rac1-deficient keratinocytes showed reduced levels of p53, γ-H2AX and p-Chk1 suggesting an attenuated DNA damage response upon UV-irradiation. Taken together, our data provide direct evidence for a protective role of Rac1 in UV-light-induced skin carcinogenesis and keratinocyte apoptosis probably through regulating mechanisms of the DNA damage response and repair pathways.
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