Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer

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

Research output: Contribution to journalArticle

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 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.

Original languageEnglish
Pages (from-to)3242-3256
Number of pages15
JournalCell Reports
Volume18
Issue number13
DOIs
Publication statusPublished - Mar 28 2017

Keywords

  • alternative splicing
  • CDK7
  • EOC
  • fimbriae
  • OSE
  • ovarian cancer
  • phosphoproteomics
  • POLR2A
  • quantitative proteomics
  • THZ1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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