ArticleThe Journal of clinical investigation2010
Cytoplasmic p21 expression levels determine cisplatin resistance in human testicular cancer.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
116 citing papers in PubMed, 2 syntheses or guidelines pooled it, 232 citations in OpenAlex.
- Germline and Somatic Genetic Variants in the p53 Pathway Interact to Affect Cancer Risk, Progression, and Drug Response.Cancer research · 2021Pooled it
- Meta-analysis identifies four new loci associated with testicular germ cell tumor.Nature genetics · 2013Pooled it
- MicroRNAs and immunotherapy in testicular germ cell tumors: opportunities and challenges for modulation of the immune microenvironment.Frontiers in immunology · 2026Review
- The AKT-p21 phosphorylation signaling axis confers poor prognosis and dacarbazine resistance in melanoma.Scientific reports · 2025Article
- CDKN1A and cellular senescence are associated with immune resistance in advanced lung adenocarcinoma.Clinical and experimental medicine · 2025Article
- Exploring the molecular pathways of miRNAs in testicular cancer: from diagnosis to therapeutic innovations.Functional & integrative genomics · 2025Review
- Harnessing the power of miRNAs for precision diagnosis and treatment of male infertility.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors and potential therapeutic agents (Review).Experimental and therapeutic medicine · 2025Review
- Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- Death associated protein like 1 acts as a novel tumor suppressor in melanoma by increasing the stability of P21 protein.Molecular and cellular biochemistry · 2025Article
- Cisplatin resistance in head and neck squamous cell carcinoma is linked to DNA damage response and cell cycle arrest transcriptomics rather than poor drug uptake.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Distinct adaptive strategies to cisplatin, vinblastine and gemcitabine in a panel of chemoresistant bladder cancer cell lines.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Folate Receptor Alpha-A Novel Approach to Cancer Therapy.International journal of molecular sciences · 2024Review
- Pure testicular choriocarcinoma, a rare and highly malignant subtype with challenging treatment: A case report and review of the literature.Molecular and clinical oncology · 2024Article
- Alteration in the expression of the chemotherapy resistance‑related genes in response to chronic and acute hypoxia in pancreatic cancer.Biomedical reports · 2023Article
- p21 promotes gemcitabine tolerance in A549 cells by inhibiting DNA damage and altering the cell cycle.Oncology letters · 2023Article
- p53-Dependent Cytoprotective Mechanisms behind Resistance to Chemo-Radiotherapeutic Agents Used in Cancer Treatment.Cancers · 2023Review
- Differentially Expressed Genes Induced by Erythropoietin Receptor Overexpression in Rat Mammary Adenocarcinoma RAMA 37-28 Cells.International journal of molecular sciences · 2023Article
- Article
- Targeting CLDN6 in germ cell tumors by an antibody-drug-conjugate and studying therapy resistance of yolk-sac tumors to identify and screen specific therapeutic options.Molecular medicine (Cambridge, Mass.) · 2023Article
56 more citing papers are in PubMed but not listed here.
Corrections and comments
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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
Platinum-based chemotherapies such as cisplatin are used as first-line treatment for many cancers. Although there is often a high initial responsiveness, the majority of patients eventually relapse with platinum-resistant disease. For example, a subset of testicular cancer patients still die even though testicular cancer is considered a paradigm of cisplatin-sensitive solid tumors, but the mechanisms of chemoresistance remain elusive. Here, we have shown that one key determinant of cisplatin-resistance in testicular embryonal carcinoma (EC) is high cytoplasmic expression of the cyclin-dependent kinase (CDK) inhibitor p21. The EC component of the majority of refractory testicular cancer patients exhibited high cytoplasmic p21 expression, which protected EC cell lines against cisplatin-induced apoptosis via CDK2 inhibition. Localization of p21 in the cytoplasm was critical for cisplatin resistance, since relocalization of p21 to the nucleus by Akt inhibition sensitized EC cell lines to cisplatin. We also demonstrated in EC cell lines and human tumor tissue that high cytoplasmic p21 expression and cisplatin resistance of EC were inversely associated with the expression of Oct4 and miR-106b seed family members. Thus, targeting cytoplasmic p21, including by modulation of the Oct4/miR-106b/p21 pathway, may offer new strategies for the treatment of chemoresistant testicular and other types of cancer.
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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 Socratic graph.