ArticleCell death & disease2011
Disruption of the MDM2-p53 interaction strongly potentiates p53-dependent apoptosis in cisplatin-resistant human testicular carcinoma cells via the Fas/FasL pathway.
Article in Cell death & disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers: IV: Current and Future Utilization of Molecular-Genetic Tests for Testicular Germ Cell Tumors.The American journal of surgical pathology · 2020Guideline
- Role of the MDM2/p53 axis in regulating cisplatin response in tumor cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors and potential therapeutic agents (Review).Experimental and therapeutic medicine · 2025Review
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- Targeting MDM2-p53 interaction for breast cancer therapy.Oncology research · 2025Review
- Article
- The New Tumour Biomarker miRNA-371-3p Influences Cisplatin Sensitivity of Testicular Germ Cell Tumour Cell Lines.Journal of cellular and molecular medicine · 2024Article
- A testis-specific lncRNA functions as a post-transcriptional regulator of MDM2 and stimulates apoptosis of testicular germ cell tumor cells.Cell death discovery · 2024Article
- Folate Receptor Alpha-A Novel Approach to Cancer Therapy.International journal of molecular sciences · 2024Review
- MDM2- an indispensable player in tumorigenesis.Molecular biology reports · 2023Review
- Breaking the Mold: Epigenetics and Genomics Approaches Addressing Novel Treatments and Chemoresponse in TGCT Patients.International journal of molecular sciences · 2023Review
- Overcoming Chemotherapy Resistance in Germ Cell Tumors.Biomedicines · 2022Review
- Genomic features of mediastinal germ cell tumors: a narrative review.Mediastinum (Hong Kong, China) · 2022Review
- Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?Cellular & molecular biology letters · 2021Review
- The Role ofInternational journal of molecular sciences · 2021Article
- The Enigmatic Role of TP53 in Germ Cell Tumours: Are We Missing Something?International journal of molecular sciences · 2021Review
- Folate receptor α increases chemotherapy resistance through stabilizing MDM2 in cooperation with PHB2 that is overcome by MORAb-202 in gastric cancer.Clinical and translational medicine · 2021Article
- Mechanisms of TP53 Pathway Inactivation in Embryonic and Somatic Cells-Relevance for Understanding (Germ Cell) Tumorigenesis.International journal of molecular sciences · 2021Review
- Toxicity and Anti-Proliferative Properties ofLife (Basel, Switzerland) · 2021Article
- Establishment and characterisation of testicular cancer patient-derived xenograft models for preclinical evaluation of novel therapeutic strategies.Scientific reports · 2020Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Wild-type p53 has a major role in the response and execution of apoptosis after chemotherapy in many cancers. Although high levels of wild-type p53 and hardly any TP53 mutations are found in testicular cancer (TC), chemotherapy resistance is still observed in a significant subgroup of TC patients. In the present study, we demonstrate that p53 resides in a complex with MDM2 at higher cisplatin concentrations in cisplatin-resistant human TC cells compared with cisplatin-sensitive TC cells. Inhibition of the MDM2-p53 interaction using either Nutlin-3 or MDM2 RNA interference resulted in hyperactivation of the p53 pathway and a strong induction of apoptosis in cisplatin-sensitive and -resistant TC cells. Suppression of wild-type p53 induced resistance to Nutlin-3 in TC cells, demonstrating the key role of p53 for Nutlin-3 sensitivity. More specifically, our results indicate that p53-dependent induction of Fas membrane expression (∼threefold) and enhanced Fas/FasL interactions at the cell surface are important mechanisms of Nutlin-3-induced apoptosis in TC cells. Importantly, an analogous Fas-dependent mechanism of apoptosis upon Nutlin-3 treatment is executed in wild-type p53 expressing Hodgkin lymphoma and acute myeloid leukaemia cell lines. Finally, we demonstrate that Nutlin-3 strongly augmented cisplatin-induced apoptosis and cell kill via the Fas death receptor pathway. This effect is most pronounced in cisplatin-resistant TC cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.