دورية أكاديمية
Pan-Cancer landscape of protein activities identifies drivers of signalling dysregulation and patient survival
| العنوان: | Pan-Cancer landscape of protein activities identifies drivers of signalling dysregulation and patient survival |
|---|---|
| المؤلفون: | Sousa, Abel, Dugourd, Aurelien, Memon, Danish, Petursson, Borgthor, Petsalaki, Evangelia, Saez-Rodriguez, Julio, Beltrao, Pedro, id_orcid:0 000-0002-2724-7703 |
| المصدر: | Molecular Systems Biology, 19 (3) |
| بيانات النشر: | Nature |
| سنة النشر: | 2023 |
| المجموعة: | ETH Zürich Research Collection |
| مصطلحات موضوعية: | adaptation, cancer genomics, cell signalling, phosphoproteomics, protein activities |
| الوصف: | Genetic alterations in cancer cells trigger oncogenic transformation, a process largely mediated by the dysregulation of kinase and transcription factor (TF) activities. While the mutational profiles of thousands of tumours have been extensively characterised, the measurements of protein activities have been technically limited until recently. We compiled public data of matched genomics and (phospho)proteomics measurements for 1,110 tumours and 77 cell lines that we used to estimate activity changes in 218 kinases and 292 TFs. Co-regulation of kinase and TF activities reflects previously known regulatory relationships and allows us to dissect genetic drivers of signalling changes in cancer. We find that loss-of-function mutations are not often associated with the dysregulation of downstream targets, suggesting frequent compensatory mechanisms. Finally, we identified the activities most differentially regulated in cancer subtypes and showed how these can be linked to differences in patient survival. Our results provide broad insights into the dysregulation of protein activities in cancer and their contribution to disease severity. ; ISSN:1744-4292 |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/application/pdf |
| اللغة: | English |
| العلاقة: | http://hdl.handle.net/20.500.11850/603777Test |
| DOI: | 10.3929/ethz-b-000603777 |
| الإتاحة: | https://doi.org/20.500.11850/603777Test https://doi.org/10.3929/ethz-b-000603777Test https://doi.org/10.15252/msb.202110631Test https://hdl.handle.net/20.500.11850/603777Test |
| حقوق: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0Test/ ; Creative Commons Attribution 4.0 International |
| رقم الانضمام: | edsbas.8BAD8E62 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3929/ethz-b-000603777 |
|---|