Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer

31Citations
Citations of this article
114Readers
Mendeley users who have this article in their library.

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.

Cite

CITATION STYLE

APA

Francavilla, C., Lupia, M., Tsafou, K., Villa, A., Kowalczyk, K., Rakownikow Jersie-Christensen, R., … Olsen, J. V. (2017). Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer. Cell Reports, 18(13), 3242–3256. https://doi.org/10.1016/j.celrep.2017.03.015

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free