MDM4 is a key therapeutic target in cutaneous melanoma
| العنوان: | MDM4 is a key therapeutic target in cutaneous melanoma |
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| المؤلفون: | Sue Haupt, Ygal Haupt, Jean-Christophe Marine, Michael Dewaele, Aart G. Jochemsen, Elisabeth A. Russell, Roger S. Lo, Stephanie Villar, Flavie Luciani, Hubing Shi, Federico Bernal, Clare G Fedele, Mark Shackleton, Aleksandra Zwolinska, Lionel Larue, Dana Yip, Agnieszka Gembarska, Job de Lange, James S. Goydos, Gatien Moriceau, Ghanem Elias Ghanem, Jody J. Haigh |
| المساهمون: | Human genetics, CCA - Oncogenesis |
| المصدر: | Gembarska, A, Luciani, F, Fedele, C, Russell, E A, Dewaele, M, Villar, S, Zwolinska, A, Haupt, S, de Lange, J, Yip, D, Goydos, J, Haigh, J J, Haupt, Y, Larue, L, Jochemsen, A, Shi, H, Moriceau, G, Lo, R S, Ghanem, G, Shackleton, M, Bernal, F & Marine, J-C 2012, ' MDM4 is a key therapeutic target in cutaneous melanoma ', Nature Medicine, vol. 18, no. 8, pp. 1239-1247 . https://doi.org/10.1038/nm.2863Test Nature Medicine, 18(8), 1239 Nature Medicine, 18(8), 1239-1247. Nature Publishing Group |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Keratinocytes, Male, Neuroblastoma RAS viral oncogene homolog, Skin Neoplasms, Melanoma, Experimental, Apoptosis, Cell Cycle Proteins, Cell-Penetrating Peptides, medicine.disease_cause, GTP Phosphohydrolases, Mice, Melanoma, Tumor Stem Cell Assay, Nuclear Proteins, Proto-Oncogene Proteins c-mdm2, General Medicine, Neoplasm Proteins, Up-Regulation, Gene Expression Regulation, Neoplastic, Melanocytes, Female, Signal Transduction, Proto-Oncogene Proteins B-raf, Recombinant Fusion Proteins, Mice, Nude, Antineoplastic Agents, Mice, Transgenic, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Cell Line, Tumor, Proto-Oncogene Proteins, medicine, Animals, Humans, neoplasms, Oncogene, Membrane Proteins, Cancer, medicine.disease, Xenograft Model Antitumor Assays, Mice, Inbred C57BL, Drug Resistance, Neoplasm, Cutaneous melanoma, Cancer research, Tumor Suppressor Protein p53, Carcinogenesis, V600E |
| الوصف: | The inactivation of the p53 tumor suppressor pathway, which often occurs through mutations in TP53 (encoding tumor protein 53) is a common step in human cancer. However, in melanoma-A highly chemotherapy-resistant disease-TP53 mutations are rare, raising the possibility that this cancer uses alternative ways to overcome p53-mediated tumor suppression. Here we show that Mdm4 p53 binding protein homolog (MDM4), a negative regulator of p53, is upregulated in a substantial proportion (∼65%) of stage I-IV human melanomas and that melanocyte-specific Mdm4 overexpression enhanced tumorigenesis in a mouse model of melanoma induced by the oncogene Nras. MDM4 promotes the survival of human metastatic melanoma by antagonizing p53 proapoptotic function. Notably, inhibition of the MDM4-p53 interaction restored p53 function in melanoma cells, resulting in increased sensitivity to cytotoxic chemotherapy and to inhibitors of the BRAF (V600E) oncogene. Our results identify MDM4 as a key determinant of impaired p53 function in human melanoma and designate MDM4 as a promising target for antimelanoma combination therapy. © 2012 Nature America, Inc. All rights reserved. |
| اللغة: | English |
| تدمد: | 1078-8956 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d1d4067186a4320ccbd9b155e81ac59aTest https://research.vumc.nl/en/publications/532cece1-746b-413c-8211-14e34256a071Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d1d4067186a4320ccbd9b155e81ac59a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10788956 |
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