ArticleBritish journal of cancer2023
Genome-scale CRISPR screen reveals neddylation to contribute to cisplatin resistance of testicular germ cell tumours.
Article in British journal of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential.Cell death & disease · 2026Review
- The role of neddylation in colorectal cancer and its therapeutic potential.Discover oncology · 2025Review
- Epithelial‑mesenchymal plasticity and cisplatin resistance in germ cell tumors: Mechanisms and emerging therapeutic strategies (Review).International journal of oncology · 2025Review
- Identification of novel susceptibility loci for testicular germ cell tumors through multi-omics analysis.Discover oncology · 2025Article
- Integrative analysis based on CRISPR screen identifies apilimod as a potential therapeutic agent for cisplatin-induced acute kidney injury treatment.Science China. Life sciences · 2025Article
- Mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors and potential therapeutic agents (Review).Experimental and therapeutic medicine · 2025Review
- TRIM25: A Global Player of Cell Death Pathways and Promising Target of Tumor-Sensitizing Therapies.Cells · 2025Review
- Article
- LINC00470 promotes malignant progression of testicular germ cell tumors.Molecular biology reports · 2024Article
- Neddylation activated TRIM25 desensitizes triple-negative breast cancer to paclitaxel via TFEB-mediated autophagy.Journal of experimental & clinical cancer research : CR · 2024Article
- Transcriptomic comparison of in vitro models of the human placenta.bioRxiv : the preprint server for biology · 2024Article
- CRISPR-Cas and CRISPR-based screening system for precise gene editing and targeted cancer therapy.Journal of translational medicine · 2024Review
- Biomarkers for Salvage Therapy in Testicular Germ Cell Tumors.International journal of molecular sciences · 2023Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundType II testicular germ cell tumours (TGCT) are the most prevalent tumours in young men. Patients suffering from cisplatin-resistant TGCTs are facing very poor prognosis demanding novel therapeutic options. Neddylation is a known posttranslational modification mediating many important biological processes, including tumorigenesis. Overactivation of the neddylation pathway promotes carcinogenesis and tumour progression in various entities by inducing proteasomal degradation of tumour suppressors (e.g., p21, p27).
methodsWe used a genome-scale CRISPR/Cas9 activation screen to identify cisplatin resistance factors. TGCT cell lines were treated with the neddylation inhibitor (MLN4924)/cisplatin/combination and investigated for changes in viability (XTT assay), apoptosis/cell cycle (flow cytometry) as well as in the transcriptome (3'mRNA sequencing).
resultsNAE1 overexpression was detected in cisplatin-resistant colonies from the CRISPR screen. Inhibition of neddylation using MLN4924 increased cisplatin cytotoxicity in TGCT cell lines and sensitised cisplatin-resistant cells towards cisplatin. Apoptosis, G2/M-phase cell cycle arrest, γH2A.X/P27 accumulation and mesoderm/endoderm differentiation were observed in TGCT cells, while fibroblast cells were unaffected.
conclusionsWe identified overactivation of neddylation as a factor for cisplatin resistance in TGCTs and highlighted the additive effect of NAE1 inhibition by MLN4924 in combination with cisplatin as a novel treatment option for TGCTs.
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