ArticleCell cycle (Georgetown, Tex.)2014
Loss of Notch1-dependent p21(Waf1/Cip1) expression influences the Notch1 outcome in tumorigenesis.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- The Multifaceted Role of Keratinocytes in Hidradenitis Suppurativa Pathogenesis.Experimental dermatology · 2026Review
- MAML1 drives Notch and Hedgehog oncogenic pathways by inhibiting Itch activity in triple-negative breast cancer.Cell death and differentiation · 2026Article
- AntagomiR-192-5p-engineered exosomes encapsulated in MXene-modified GelMA hydrogel facilitated epithelization of burn wounds by targeting OLFM4.Bioactive materials · 2025Article
- Stem cells, Notch-1 signaling, and oxidative stress: a hellish trio in cancer development and progression within the airways. Is there a role for natural compounds?Carcinogenesis · 2024Review
- Article
- 5FU/Oxaliplatin-Induced Jagged1 Cleavage Counteracts Apoptosis Induction in Colorectal Cancer: A Novel Mechanism of Intrinsic Drug Resistance.Frontiers in oncology · 2022Article
- miR-125b/NRF2/HO-1 axis is involved in protection against oxidative stress of cystic fibrosis: A pilot study.Experimental and therapeutic medicine · 2021Article
- Functional cooperation between ASK1 and p21Cell death discovery · 2021Article
- Notch3 contributes to T-cell leukemia growth via regulation of the unfolded protein response.Oncogenesis · 2020Article
- Review
- In vivo and in vitro inhibition of osteosarcoma growth by the pan Bcl-2 inhibitor AT-101.Investigational new drugs · 2020Article
- Article
- Mesenchymal Stem/Progenitor Cells: The Prospect of Human Clinical Translation.Stem cells international · 2020Review
- A Dynamic Role of Mastermind-Like 1: A Journey Through the Main (Path)ways Between Development and Cancer.Frontiers in cell and developmental biology · 2020Review
- PLK1 targets NOTCH1 during DNA damage and mitotic progression.The Journal of biological chemistry · 2019Article
- Notch Signaling Activation as a Hallmark for Triple-Negative Breast Cancer Subtype.Journal of oncology · 2019Review
- Optimization of Protein-Protein Interaction Measurements for Drug Discovery Using AFM Force Spectroscopy.IEEE transactions on nanotechnology · 2019Article
- Wnt, Notch, and TGF-β Pathways Impinge on Hedgehog Signaling Complexity: An Open Window on Cancer.Frontiers in genetics · 2019Review
- Histone Modifications Drive Aberrant Notch3 Expression/Activity and Growth in T-ALL.Frontiers in oncology · 2019Article
- Yeast-Based Screen to Identify Natural Compounds with a Potential Therapeutic Effect in Hailey-Hailey Disease.International journal of molecular sciences · 2018Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notch signaling plays a complex role in carcinogenesis, and its signaling pathway has both tumor-suppressor and oncogenic components. In this study we investigated the effects of reactive oxygen species (ROS) on Notch1 signaling outcome in keratinocyte biology. We demonstrate that Notch1 function contributes to the arsenic-induced keratinocyte transformation. We found that acute exposure to arsenite increases oxidative stress and inhibits proliferation of keratinocyte cells by upregulation of p21(waf1/Cip1). The necessity of p21(waf1/Cip1) for arsenite-induced cell death was demonstrated by targeted downregulation of p21(waf1/Cip1) by using RNA interference. We further demonstrated that on acute exposure to arsenite, p21(waf1/Cip1) is upregulated and Notch1 downmodulated, whereas on chronic exposure to arsenite, malignant progression of arsenite-treated keratinocytes cells was accompanied by regained expression and activity of Notch1. Notch1 activity in arsenite-transformed keratinocytes inhibits arsenite-induced upregulation of p21(waf1/Cip1) by sustaining c-myc expression. We further demonstrated that c-myc collaborates with Nrf2, a key regulator for the maintenance of redox homeostasis, to promote metabolic activities that support cell proliferation and cytoprotection. Therefore, Notch1-mediated repression of p21(waf1/Cip1) expression results in the inhibition of cell death and keratinocytes transformation. Our results not only demonstrate that sustained Notch1 expression is at least one key event implicated in the arsenite human skin carcinogenic effect, but also may provide mechanistic insights into the molecular aspects that determine whether Notch signaling will be either oncogenic or tumor suppressive.
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