ArticleCell death and differentiation2023
Cisplatin-induced cell death increases the degradation of the MRE11-RAD50-NBS1 complex through the autophagy/lysosomal pathway.
Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- FBXW7 Gene Mutation and Expression in Colorectal Cancer (CRC): A Systematic Review from Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2025Pooled it
- Engineered nanodendritic sonosensitizers empower sonodynamic-elicited ferroptosis and PANoptosis against platinum-resistant breast cancer.Materials today. Bio · 2026Article
- BTAF1: a key regulator of DNA end resection and predictor of chemotherapy sensitivity in gastric cancer.Cell death and differentiation · 2026Article
- Molecular Insights from Differential Proteomic Profiling of Premalignant Cervical Lesions and Cervical Cancer.Pathogens (Basel, Switzerland) · 2026Article
- hSpindly dynamics modulate spindle assembly checkpoint signaling, promoting resistance to mitotic inhibitors.iScience · 2026Article
- β-TrCP overexpression enhances cisplatin sensitivity by depleting BRCA1.Molecular oncology · 2026Article
- βTrCP facilitates MRN complex localization on chromatin to enhance DNA repair.Communications biology · 2025Article
- Identification and validation of platinum resistance signature in gastric cancer.Cancer cell international · 2025Article
- Overexpression of βTrCP1 elicits cell death in cisplatin-induced senescent cells.Cell death & disease · 2025Article
- Molecular Subtyping of Hepatocellular Carcinoma via Lysosome-Related Genes for Prognosis and Therapy Prediction.International journal of general medicine · 2025Article
- Celastrol reduces cisplatin-induced nephrotoxicity by downregulating SNORD3A level in kidney organoids derived from human iPSCs.Frontiers in pharmacology · 2025Article
- Insights from a Computational-Based Approach for Analyzing Autophagy Genes across Human Cancers.Genes · 2023Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cisplatin and other platinum-based anticancer agents are among the most widely used chemotherapy drugs in the treatment of different types of cancer. However, it is common to find patients who respond well to treatment at first but later relapse due to the appearance of resistance to cisplatin. Among the mechanisms responsible for this phenomenon is the increase in DNA damage repair. Here, we elucidate the effect of cisplatin on the MRN (MRE11-RAD50-NBS1) DNA damage sensor complex. We found that the tumor suppressor FBXW7 is a key factor in controlling the turnover of the MRN complex by inducing its degradation through lysosomes. Inhibition of lysosomal enzymes allowed the detection of the association of FBXW7-dependent ubiquitylated MRN with LC3 and the autophagy adaptor p62/SQSTM1 and the localization of MRN in lysosomes. Furthermore, cisplatin-induced cell death increased MRN degradation, suggesting that this complex is one of the targets that favor cell death. These findings open the possibility of using the induction of the degradation of the MRN complex after genotoxic damage as a potential therapeutic strategy to eliminate tumor cells.
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