ArticleProceedings of the National Academy of Sciences of the United States of America2017
Repair shielding of platinum-DNA lesions in testicular germ cell tumors by high-mobility group box protein 4 imparts cisplatin hypersensitivity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed, 51 citations in OpenAlex.
- Dualistic Roles of High Mobility Group Box 1 in Cancer and Inflammation.Cancer medicine · 2025Review
- Engineering biomimetic nanosystem targeting multiple tumor radioresistance hallmarks for enhanced radiotherapy.Science China. Life sciences · 2024Article
- HMGB1/RAGE axis in tumor development: unraveling its significance.Frontiers in oncology · 2024Review
- Detection of oxaliplatin- and cisplatin-DNA lesions requires different global genome repair mechanisms that affect their clinical efficacy.NAR cancer · 2023Article
- Evolutionary determinants of curability in cancer.Nature ecology & evolution · 2023Review
- Breaking the Mold: Epigenetics and Genomics Approaches Addressing Novel Treatments and Chemoresponse in TGCT Patients.International journal of molecular sciences · 2023Review
- Platinum-Based Regimens Are Active in Advanced Pediatric-Type Rhabdomyosarcoma in Adults and Depending on HMGB1 Expression.International journal of molecular sciences · 2023Article
- Overcoming Chemotherapy Resistance in Germ Cell Tumors.Biomedicines · 2022Review
- The role of high mobility group protein B3 (HMGB3) in tumor proliferation and drug resistance.Molecular and cellular biochemistry · 2021Review
- Between a Rock and a Hard Place: An Epigenetic-Centric View of Testicular Germ Cell Tumors.Cancers · 2021Review
- Deficiency of the novel high mobility group protein HMGXB4 protects against systemic inflammation-induced endotoxemia in mice.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Emergence of spatio-temporal variations in chemotherapeutic drug efficacy: in-vitro and in-Silico 3D tumour spheroid studies.BMC cancer · 2020Article
- Role of Nucleotide Excision Repair in Cisplatin Resistance.International journal of molecular sciences · 2020Review
- Cisplatin Resistance in Testicular Germ Cell Tumors: Current Challenges from Various Perspectives.Cancers · 2020Review
- CRISPR/Cas9 for overcoming drug resistance in solid tumors.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2020Review
- Article
- Germline genome protection: implications for gamete quality and germ cell tumorigenesis.Andrology · 2019Review
- Testicular germ cell tumor: a comprehensive review.Cellular and molecular life sciences : CMLS · 2019Review
- Mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors.Cancer drug resistance (Alhambra, Calif.) · 2019Article
- Effect of in vivo post-translational modifications of the HMGB1 protein upon binding to platinated DNA: a molecular simulation study.Nucleic acids research · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cisplatin is the most commonly used anticancer drug for the treatment of testicular germ cell tumors (TGCTs). The hypersensitivity of TGCTs to cisplatin is a subject of widespread interest. Here, we show that high-mobility group box protein 4 (HMGB4), a protein preferentially expressed in testes, uniquely blocks excision repair of cisplatin-DNA adducts, 1,2-intrastrand cross-links, to potentiate the sensitivity of TGCTs to cisplatin therapy. We used CRISPR/Cas9-mediated gene editing to knockout the HMGB4 gene in a testicular human embryonic carcinoma and examined cellular responses. We find that loss of HMGB4 elicits resistance to cisplatin as evidenced by cell proliferation and apoptosis assays. We demonstrate that HMGB4 specifically inhibits repair of the major cisplatin-DNA adducts in TGCT cells by using the human TGCT excision repair system. Our findings also reveal characteristic HMGB4-dependent differences in cell cycle progression following cisplatin treatment. Collectively, these data provide convincing evidence that HMGB4 plays a major role in sensitizing TGCTs to cisplatin, consistent with shielding of platinum-DNA adducts from excision repair.
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Registered trials
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.