Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer

Chiara Francavilla, Michela Lupia, Kalliopi P Tsafou, Alessandra Villa, Katarzyna Kowalczyk, Rosa Rakownikow Jersie-Christensen, Giovanni Bertalot, Stefano Confalonieri, Søren Brunak, Lars J Jensen, Ugo Cavallaro, Jesper V Olsen

Research output: Contribution to journalArticlepeer-review

Abstract

Our understanding of the molecular determinants of cancer is still inadequate because of cancer heterogeneity. Here, using epithelial ovarian cancer (EOC) as a model system, we analyzed minute amount of patient-derived epithelial cells from either healthy or cancer tissues by single-shot mass-spectrometry-based phosphoproteomics. Using a multi-disciplinary approach we demonstrated that primary cells recapitulate tissue complexity and represent a valuable source of differentially expressed proteins and phosphorylation sites that discriminate cancer from healthy cells. Finally, we uncovered previously unknown kinase signatures associated to EOC. In particular, CDK7 targets were characterized in both EOC primary cells and ovarian cancer cell lines. We showed that CDK7 controls cell proliferation and that pharmacological inhibition of CDK7 selectively represses EOC cell proliferation. Our approach defines the molecular landscape of EOC, paving the way for efficient therapeutic approaches for patients. Furthermore, we highlight the potential of phosphoproteomics to identify clinically relevant and druggable pathways in cancer.
Original languageEnglish
Pages (from-to)3242-3256
Number of pages15
JournalCell Reports
Volume18
Issue number13
Early online date28 Mar 2017
DOIs
Publication statusPublished - 28 Mar 2017

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