Dual functions of SPOP and ERG dictate androgen therapy responses in prostate cancer
| العنوان: | Dual functions of SPOP and ERG dictate androgen therapy responses in prostate cancer |
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| المؤلفون: | Francesco Bertoni, Steven A. Carr, Manuela Cavalli, Holger Moch, Anna Rinaldi, Arianna Vallerga, Azzurra Mutti, Tanya Svinkina, Ze Dong, Hana Janouskova, Geniver El Tekle, Tiziano Bernasocchi, Simon Linder, Giuseppina M. Carbone, Daniela Bossi, Marianna Kruithof-de Julio, Roger Geiger, Laura P. Brandt, Wilbert Zwart, Andrea Rinaldi, Simone Mosole, Marita Zoma, Marco Bolis, Jean-Philippe Theurillat, Filippo Spriano, Andrea Alimonti, Peter Schraml, Cai-Guang Yang, Domenico Albino, Valentina Ceserani, Namrata D. Udeshi, Mark A. Rubin |
| المصدر: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-18 (2021) Bernasocchi, Tiziano; El Tekle, Geniver; Bolis, Marco; Mutti, Azzurra; Vallerga, Arianna; Brandt, Laura P.; Spriano, Filippo; Svinkina, Tanya; Zoma, Marita; Ceserani, Valentina; Rinaldi, Anna; Janouskova, Hana; Bossi, Daniela; Cavalli, Manuela; Mosole, Simone; Geiger, Roger; Dong, Ze; Yang, Cai-Guang; Albino, Domenico; Rinaldi, Andrea; ... (2021). Dual functions of SPOP and ERG dictate androgen therapy responses in prostate cancer. Nature communications, 12(1), p. 734. Nature Publishing Group 10.1038/s41467-020-20820-x <http://dx.doi.org/10.1038/s41467-020-20820-xTest> Nature Communications, 12 |
| بيانات النشر: | ETH Zurich, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Proteomics, Male, Cancer therapy, medicine.drug_class, Science, Mice, Nude, 610 Medicine & health, Cell Cycle Proteins, SPOP, medicine.disease_cause, Article, Tumour biomarkers, Prostate cancer, Mice, Transcriptional Regulator ERG, Cell Line, Tumor, medicine, Biomarkers, Tumor, Animals, Humans, Immunoprecipitation, Transcription factor, Cancer genetics, Oncogene Proteins, biology, Nuclear Proteins, Prostatic Neoplasms, Ubiquitin-Protein Ligase Complexes, medicine.disease, Androgen, Immunohistochemistry, Ubiquitin ligase, Androgen receptor, DNA-Binding Proteins, Repressor Proteins, HEK293 Cells, Androgen Therapy, Receptors, Androgen, Mutation, biology.protein, Cancer research, Carcinogenesis, 610 Medizin und Gesundheit, Co-Repressor Proteins, Protein Binding, Signal Transduction |
| الوصف: | Driver genes with a mutually exclusive mutation pattern across tumor genomes are thought to have overlapping roles in tumorigenesis. In contrast, we show here that mutually exclusive prostate cancer driver alterations involving the ERG transcription factor and the ubiquitin ligase adaptor SPOP are synthetic sick. At the molecular level, the incompatible cancer pathways are driven by opposing functions in SPOP. ERG upregulates wild type SPOP to dampen androgen receptor (AR) signaling and sustain ERG activity through degradation of the bromodomain histone reader ZMYND11. Conversely, SPOP-mutant tumors stabilize ZMYND11 to repress ERG-function and enable oncogenic androgen receptor signaling. This dichotomy regulates the response to therapeutic interventions in the AR pathway. While mutant SPOP renders tumor cells susceptible to androgen deprivation therapies, ERG promotes sensitivity to high-dose androgen therapy and pharmacological inhibition of wild type SPOP. More generally, these results define a distinct class of antagonistic cancer drivers and a blueprint toward their therapeutic exploitation. Nature Communications, 12 ISSN:2041-1723 |
| وصف الملف: | application/pdf; application/application/pdf |
| اللغة: | English |
| تدمد: | 2041-1723 |
| DOI: | 10.3929/ethz-b-000520825 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4fe8919843ab06744fd7a44c9ed8c87aTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4fe8919843ab06744fd7a44c9ed8c87a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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| DOI: | 10.3929/ethz-b-000520825 |