Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer

Publication date: 28 March 2017
Source:Cell Reports, Volume 18, Issue 13
Author(s): Chiara Francavilla, Michela Lupia, Kalliopi Tsafou, Alessandra Villa, Katarzyna Kowalczyk, Rosa Rakownikow Jersie-Christensen, Giovanni Bertalot, Stefano Confalonieri, Søren Brunak, Lars J. Jensen, Ugo Cavallaro, Jesper V. Olsen
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 a minute amount of patient-derived epithelial cells from either healthy or cancerous 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. Furthermore, we uncovered kinase signatures associated with 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. Finally, we highlight the potential of phosphoproteomics to identify clinically relevant and druggable pathways in cancer.

Graphical abstract

Teaser

Francavilla et al. use mass-spectrometry-based phosphoproteomics as a powerful tool to reveal cancer signatures. They analyze changes in the proteome and phosphoproteome of primary cells derived from epithelial ovarian cancer (EOC) compared to healthy tissues and reveal a role for the kinase CDK7 in EOC cell proliferation.


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