ArticleNucleic acids research2016
ΔNp63 activates the Fanconi anemia DNA repair pathway and limits the efficacy of cisplatin treatment in squamous cell carcinoma.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 27 citations in OpenAlex.
- Targeting PI3K inhibitor resistance in breast cancer with metabolic drugs.Signal transduction and targeted therapy · 2025Article
- A novel approach to the analysis of Overall Survival (OS) as response with Progression-Free Interval (PFI) as condition based on the RNA-seq expression data in The Cancer Genome Atlas (TCGA).BMC bioinformatics · 2024Article
- Complex and variable regulation of ΔNp63 and TAp63 by TGFβ has implications for the dynamics of squamous cell epithelial to mesenchymal transition.Scientific reports · 2024Article
- ΔNp63 Regulates Radioresistance in Human Head and Neck Squamous Carcinoma Cells.Current issues in molecular biology · 2023Article
- Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials.Signal transduction and targeted therapy · 2022Review
- Inhibition of USP28 overcomes Cisplatin-resistance of squamous tumors by suppression of the Fanconi anemia pathway.Cell death and differentiation · 2022Article
- Identifying pathways regulating the oncogenic p53 family member ΔNp63 provides therapeutic avenues for squamous cell carcinoma.Cellular & molecular biology letters · 2022Article
- DNA Demethylation Switches Oncogenic ΔNp63 to Tumor Suppressive TAp63 in Squamous Cell Carcinoma.Frontiers in oncology · 2022Article
- Review
- Epigenetic Treatment of Urothelial Carcinoma Cells Sensitizes to Cisplatin Chemotherapy and PARP Inhibitor Treatment.Cancers · 2021Article
- Anti-tumor activities ofJournal of ginseng research · 2021Article
- TP63 links chromatin remodeling and enhancer reprogramming to epidermal differentiation and squamous cell carcinoma development.Cellular and molecular life sciences : CMLS · 2020Review
- Perturbing Enhancer Activity in Cancer Therapy.Cancers · 2019Review
- IL-1β Inflammatory Cytokine-InducedInternational journal of molecular sciences · 2019Article
- Article
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Authors and funding
11 authors at 4 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
TP63, a member of the p53 gene family gene, encodes the ΔNp63 protein and is one of the most frequently amplified genes in squamous cell carcinomas (SCC) of the head and neck (HNSCC) and lungs (LUSC). Using an epiallelic series of siRNAs with intrinsically different knockdown abilities, we show that the complete loss of ΔNp63 strongly impaired cell proliferation, whereas partial ΔNp63 depletion rendered cells hypersensitive to cisplatin accompanied by an accumulation of DNA damage. Expression profiling revealed wide-spread transcriptional regulation of DNA repair genes and in particular Fanconi anemia (FA) pathway components such as FANCD2 and RAD18 - known to be crucial for the repair of cisplatin-induced interstrand crosslinks. In SCC patients ΔNp63 levels significantly correlate with FANCD2 and RAD18 expression confirming ΔNp63 as a key activator of the FA pathway in vivo Mechanistically, ΔNp63 bound an upstream enhancer of FANCD2 inactive in primary keratinocytes but aberrantly activated by ΔNp63 in SCC. Consistently, depletion of FANCD2 sensitized to cisplatin similar to depletion of ΔNp63. Together, our results demonstrate that ΔNp63 directly activates the FA pathway in SCC and limits the efficacy of cisplatin treatment. Targeting ΔNp63 therefore would not only inhibit SCC proliferation but also sensitize tumors to chemotherapy.
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