التفاصيل البيبلوغرافية
| العنوان: |
Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS G13D |
| المؤلفون: |
Kennedy, Susan A., Jarboui, Mohamed-Ali, Srihari, Sriganesh, Raso, Cinzia, Charitou, Theodosia, Herrera-Montavez, Carlos, Krstic, Aleksandar, Matallanas, David, Kiel, Christina, Rauch, Nora, Rukhlenko, Oleksii S., Kholodenko, Boris N., Iglesias-Martinez, Luis F., Ryan, Colm J., Pilkington, Ruth, Kolch, Walter |
| بيانات النشر: |
Springer |
| سنة النشر: |
2021 |
| المجموعة: |
University College Dublin: Research Repository UCD |
| مصطلحات موضوعية: |
Colorectal neoplasms, Neoplastic cell transformation, Prognosis, Survival analysis, Phosphorylation, Mutation, Proto-oncogene proteins p21(ras), bcl-Associated death protein, Protein interaction maps, ErbB receptors |
| الوصف: |
Protein-protein-interaction networks (PPINs) organize fundamental biological processes, but how oncogenic mutations impact these interactions and their functions at a network-level scale is poorly understood. Here, we analyze how a common oncogenic KRAS mutation (KRASG13D) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. Mapping >6000 PPIs shows that this network is extensively rewired in cells expressing transforming levels of KRASG13D (mtKRAS). The factors driving PPIN rewiring are multifactorial including changes in protein expression and phosphorylation. Mathematical modelling also suggests that the binding dynamics of low and high affinity KRAS interactors contribute to rewiring. PPIN rewiring substantially alters the composition of protein complexes, signal flow, transcriptional regulation, and cellular phenotype. These changes are validated by targeted and global experimental analysis. Importantly, genetic alterations in the most extensively rewired PPIN nodes occur frequently in CRC and are prognostic of poor patient outcomes. ; European Commission Horizon 2020 ; European Commission - Seventh Framework Programme (FP7) ; European Research Council ; Science Foundation Ireland ; Teagasc ; Canada Research Chair Program ; Krembil Foundation ; Ontario Research Fund ; Natural Sciences Research Council ; Canada Foundation for Innovation ; IBM ; EMBL Australia ; Canadian Cancer Society Research Institute ; Genome Canada via Ontario Genomics ; Ontario Research fund ; Consortium Québécois sur la Découverte du Médicament ; Brain Canada ; CQDM Explore ; OCE ; Tistou & Charlotte Kerstan Stiftung |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
Electronic |
| اللغة: |
English |
| تدمد: |
2041-1723 |
| العلاقة: |
Nature Communications; http://hdl.handle.net/10197/11873Test; 11; 14/IA/2395; 686098; 750688 — SAMNets; 731032; 278568; 15-CDA-3495; CRC #225404; GL2-01-030; 34876; 225404; 30865; 703889; 9427; 9428; ORF/DIG-501411 & RE08-009; 23929 |
| الإتاحة: |
http://hdl.handle.net/10197/11873Test |
| حقوق: |
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0Test/. ; https://creativecommons.org/licenses/by/3.0/ieTest/ |
| رقم الانضمام: |
edsbas.FE634F4E |
| قاعدة البيانات: |
BASE |
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