BRCA1 mutations in high-grade serous ovarian cancer are associated with proteomic changes in DNA repair, splicing, transcription regulation and signaling
| Autor: | Bradbury, Melissa, Castellvi, Josep, Méndez Fernández, Olga, Sanchez Iglesias, Jose Luis, Pérez-Benavente, Assumpció, Gil-Moreno, Antonio, Sabidó, Eduard, Santamaría, Anna, Borràs, Eva, Universitat Autònoma de Barcelona. Vall d'Hebron Institut de Recerca (VHIR) |
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| Přispěvatelé: | Institut Català de la Salut, [Bradbury M] Proteomics Unit, Centre de Regulació Genòmica, Barcelona Institute of Science and Technology (BIST), 08003 Barcelona, Spain. Universitat Pompeu Fabra, 08003 Barcelona, Spain. Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Ginecologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Borràs E, Sabidó E] Proteomics Unit, Centre de Regulació Genòmica, Barcelona Institute of Science and Technology (BIST), 08003 Barcelona, Spain. Universitat Pompeu Fabra, 08003 Barcelona, Spain. [Castellví J] Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Méndez O] Laboratori de Cicle Cel•lular i Càncer, Grup de Recerca Biomèdica en Urologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Sánchez-Iglesias JL, Pérez-Benavente A] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Ginecologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Gil-Moreno A] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Ginecologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain. [Santamaria A] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Laboratori de Cicle Cel•lular i Càncer, Grup de Recerca Biomèdica en Urologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Ovarian Neoplasms
Proteomics ADN - Reparació Multidisciplinary Genetic Phenomena::DNA Repair [PHENOMENA AND PROCESSES] DNA Repair BRCA1 Protein Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms [DISEASES] Mutació (Biologia) Genetic Phenomena::Genetic Variation::Mutation [PHENOMENA AND PROCESSES] neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas [ENFERMEDADES] Ovaris -- Càncer fenómenos genéticos::reparación del ADN [FENÓMENOS Y PROCESOS] Cystadenocarcinoma Serous Genòmica Ovaris - Càncer Ovarian cancer Mutation Humans Female fenómenos genéticos::variación genética::mutación [FENÓMENOS Y PROCESOS] Genètica |
| Zdroj: | Scientific Reports Scientia |
| Popis: | Ovarian cancer; Proteomics Cáncer de ovarios: Proteómica Càncer d'ovaris; Proteòmica Despite recent advances in the management of BRCA1 mutated high-grade serous ovarian cancer (HGSC), the physiology of these tumors remains poorly understood. Here we provide a comprehensive molecular understanding of the signaling processes that drive HGSC pathogenesis with the addition of valuable ubiquitination profiling, and their dependency on BRCA1 mutation-state directly in patient-derived tissues. Using a multilayered proteomic approach, we show the tight coordination between the ubiquitination and phosphorylation regulatory layers and their role in key cellular processes related to BRCA1-dependent HGSC pathogenesis. In addition, we identify key bridging proteins, kinase activity, and post-translational modifications responsible for molding distinct cancer phenotypes, thus providing new opportunities for therapeutic intervention, and ultimately advance towards a more personalized patient care. This work was supported by the PhD4MD collaborative research program between the Vall d’Hebron Research Institute (VHIR) and the Centre for Genomic Regulation (CRG). The CRG/UPF Proteomics Unit is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech) and it is a member of the ProteoRed PRB3 consortium which is supported by grant PT17/0019 of the PE I+D+i 2013-2016 from the Instituto de Salud Carlos III (ISCIII) and ERDF. We acknowledge support from the Spanish Ministry of Science, Innovation and Universities, (CTQ2016-80364-P and “Centro de Excelencia Severo Ochoa 2013-2017”, SEV-2012-0208), and “Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya” (2017SGR595 and 2017SGR1661). This project has also received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 823839 (EPIC-XS). It has also been supported by grants from the Instituto Carlos III (PI15/00238, PI18/01017, PI21/00977), the Miguel Servet Program (CP13/00158 and CPII18/00027) and the Ministerio de Economía y Competitividad y Fondos FEDER (RTC-2015-3821-1). The authors are grateful to the team members of the Proteomics Unit at the Centre for Genomic Regulation, the Biomedical Research Group in Gynecology at the Vall d’Hebron Institute, the Gynecological Oncology Unit at the Vall d’Hebron Hospital and the Biomedical Research Group in Urology at the Vall d’Hebron Institute for their assistance. |
| Databáze: | OpenAIRE |
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