Author:
Bradbury Melissa,Borràs Eva,Castellví Josep,Méndez Olga,Sánchez-Iglesias José Luis,Pérez-Benavente Assumpció,Gil-Moreno Antonio,Sabidó Eduard,Santamaria Anna
Abstract
AbstractDespite 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.
Funder
PhD4MD Research Grant
Instituto de Salud Carlos III
Agència de Gestió d'Ajuts Universitaris i de Recerca
Ministerio de Economía y Competitividad
Publisher
Springer Science and Business Media LLC
Cited by
2 articles.
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