BRCA1 mutations in high-grade serous ovarian cancer are associated with proteomic changes in DNA repair, splicing, transcription regulation and signaling

Melissa Bradbury, Josep Castellvi, Olga Méndez Fernández, Jose Luis Sanchez Iglesias, Assumpció Pérez-Benavente, Antonio Gil-Moreno, Eduard Sabidó, Anna Santamaría, Eva Borràs

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Resumen

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.
Idioma originalInglés
PublicaciónScientific Reports
Volumen12
DOI
EstadoPublicada - 2022

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