ArticleCell death and differentiation2022
Inhibition of USP28 overcomes Cisplatin-resistance of squamous tumors by suppression of the Fanconi anemia pathway.
Article in Cell death and differentiation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Loss of KDM6A-mediated genomic instability and metabolic reprogramming regulates response to therapeutic perturbations in bladder cancer.Nature communications · 2026Article
- Multidimensional analysis of deubiquitinating enzymes in colorectal cancer: biological mechanisms and targeted therapeutic strategies.Frontiers in oncology · 2026Review
- USP28 Promotes Osimertinib Resistance in H1975 NSCLC Cells by Deubiquitinating and Stabilizing SIRT1.The Kaohsiung journal of medical sciences · 2026Article
- A novel feedback loop between DYRK2 and USP28 regulates cancer homeostasis and DNA damage signaling.Cell death and differentiation · 2026Article
- E3 ubiquitin ligases orchestrate chemo-resistance in gastrointestinal malignancies: from DNA damage response to therapeutic targeting.Frontiers in oncology · 2026Review
- Decoding the ubiquitin network: molecular mechanisms and therapeutic vulnerabilities for precision radio-sensitization in cancer.Molecular cancer · 2025Review
- Article
- USP28 promotes PARP inhibitor resistance by enhancing SOX9-mediated DNA damage repair in ovarian cancer.Cell death & disease · 2025Article
- The deubiquitinase USP44 enhances cisplatin chemosensitivity through stabilizing STUB1 to promote LRPPRC degradation in neuroblastoma.Neuro-oncology · 2025Article
- TIP60 enhances cisplatin resistance via regulating ΔNp63α acetylation in SCC.Cell death & disease · 2024Article
- USP10 drives cancer stemness and enables super-competitor signalling in colorectal cancer.Oncogene · 2024Article
- The dimeric deubiquitinase USP28 integrates 53BP1 and MYC functions to limit DNA damage.Nucleic acids research · 2024Article
- USP28 promotes tumorigenesis and cisplatin resistance by deubiquitinating MAST1 protein in cancer cells.Cellular and molecular life sciences : CMLS · 2024Article
- Article
- USP28 controls SREBP2 and the mevalonate pathway to drive tumour growth in squamous cancer.Cell death and differentiation · 2023Article
- The dual role of p63 in cancer.Frontiers in oncology · 2023Review
- Deep transfer learning of cancer drug responses by integrating bulk and single-cell RNA-seq data.Nature communications · 2022Article
- Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials.Signal transduction and targeted therapy · 2022Review
- Ubiquitin-specific protease 28 deubiquitinates TCF7L2 to govern the action of the Wnt signaling pathway in hepatic carcinoma.Cancer science · 2022Article
- RNF4~RGMb~BMP6 axis required for osteogenic differentiation and cancer cell survival.Cell death & disease · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Squamous cell carcinomas (SCC) frequently have an exceptionally high mutational burden. As consequence, they rapidly develop resistance to platinum-based chemotherapy and overall survival is limited. Novel therapeutic strategies are therefore urgently required. SCC express ∆Np63, which regulates the Fanconi Anemia (FA) DNA-damage response in cancer cells, thereby contributing to chemotherapy-resistance. Here we report that the deubiquitylase USP28 is recruited to sites of DNA damage in cisplatin-treated cells. ATR phosphorylates USP28 and increases its enzymatic activity. This phosphorylation event is required to positively regulate the DNA damage repair in SCC by stabilizing ∆Np63. Knock-down or inhibition of USP28 by a specific inhibitor weakens the ability of SCC to cope with DNA damage during platin-based chemotherapy. Hence, our study presents a novel mechanism by which ∆Np63 expressing SCC can be targeted to overcome chemotherapy resistance. Limited treatment options and low response rates to chemotherapy are particularly common in patients with squamous cancer. The SCC specific transcription factor ∆Np63 enhances the expression of Fanconi Anemia genes, thereby contributing to recombinational DNA repair and Cisplatin resistance. Targeting the USP28-∆Np63 axis in SCC tones down this DNA damage response pathways, thereby sensitizing SCC cells to cisplatin treatment.
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