ArticlePloS one2014
Inhibition of p38 MAPK signaling augments skin tumorigenesis via NOX2 driven ROS generation.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 44 citations in OpenAlex.
- The Association between NADPH Oxidase 2 (NOX2) and Drug Resistance in Cancer.Current cancer drug targets · 2024Review
- NADPH Oxidase 2 Has a Crucial Role in Cell Cycle Progression of Esophageal Squamous Cell Carcinoma.Annals of surgical oncology · 2022Article
- The Histone Demethylase HR Suppresses Breast Cancer Development through Enhanced CELF2 Tumor Suppressor Activity.Cancers · 2022Article
- HMGB1 knockdown increases the radiosensitivity of esophageal squamous cell carcinoma by regulating the expression of molecules involved in DNA repair.Oncology letters · 2021Article
- Therapeutic wavelengths of ultraviolet B radiation activate apoptotic, circadian rhythm, redox signalling and key canonical pathways in psoriatic epidermis.Redox biology · 2021Article
- Exome sequencing identifies novel mutation signatures of UV radiation and trichostatin A in primary human keratinocytes.Scientific reports · 2020Article
- MsrA Suppresses Inflammatory Activation of Microglia and Oxidative Stress to Prevent Demyelination via Inhibition of the NOX2-MAPKs/NF-κB Signaling Pathway.Drug design, development and therapy · 2020Article
- Aloin Inhibits the Proliferation and Migration of Gastric Cancer Cells by Regulating NOX2-ROS-Mediated Pro-Survival Signal Pathways.Drug design, development and therapy · 2020Article
- Identification of master regulator genes of UV response and their implications for skin carcinogenesis.Carcinogenesis · 2019Article
- Emerging Perspective: Role of Increased ROS and Redox Imbalance in Skin Carcinogenesis.Oxidative medicine and cellular longevity · 2019Review
- The protein kinase p38α destabilizes p63 to limit epidermal stem cell frequency and tumorigenic potential.Science signaling · 2018Article
- SOX9 Transcriptionally Regulates mTOR-Induced Proliferation of Basal Cell Carcinomas.The Journal of investigative dermatology · 2018Article
- Involvement of NADPH oxidase 1 in UVB-induced cell signaling and cytotoxicity in human keratinocytes.Biochemistry and biophysics reports · 2018Article
- SIRT1 activation mediates heat-induced survival of UVB damaged Keratinocytes.BMC dermatology · 2017Article
- Molecular signaling cascades involved in nonmelanoma skin carcinogenesis.The Biochemical journal · 2016Review
- Reactive Oxygen Species and Targeted Therapy for Pancreatic Cancer.Oxidative medicine and cellular longevity · 2016Review
- Roles of p38α mitogen-activated protein kinase in mouse models of inflammatory diseases and cancer.The FEBS journal · 2015Review
- Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways.Toxicology and applied pharmacology · 2014Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
p38 mitogen-activated protein kinases (MAPKs) respond to a wide range of extracellular stimuli. While the inhibition of p38 signaling is implicated in the impaired capacity to repair ultraviolet (UV)-induced DNA damage-a primary risk factor for human skin cancers-its mechanism of action in skin carcinogenesis remains unclear, as both anti-proliferative and survival functions have been previously described. In this study, we utilized cultured keratinocytes, murine tumorigenesis models, and human cutaneous squamous cell carcinoma (SCC) specimens to assess the effect of p38 in this regard. UV irradiation of normal human keratinocytes increased the expression of all four p38 isoforms (α/β/γ/δ); whereas irradiation of p53-deficient A431 keratinocytes derived from a human SCC selectively decreased p38α, without affecting other isoforms. p38α levels are decreased in the majority of human cutaneous SCCs assessed by tissue microarray, suggesting a tumor-suppressive effect of p38α in SCC pathogenesis. Genetic and pharmacological inhibition of p38α and in A431 cells increased cell proliferation, which was in turn associated with increases in NAPDH oxidase (NOX2) activity as well as intracellular reactive oxygen species (ROS). These changes led to enhanced invasiveness of A431 cells as assessed by the matrigel invasion assay. Chronic treatment of p53-/-/SKH-1 mice with the p38 inhibitor SB203580 accelerated UV-induced SCC carcinogenesis and increased the expression of NOX2. NOX2 knockdown suppressed the augmented growth of A431 xenografts treated with SB203580. These findings indicate that in the absence of p53, p38α deficiency drives SCC growth and progression that is associated with enhanced NOX2 expression and ROS formation.
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