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.

Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer / Francavilla, C; Lupia, M; Tsafou, K; Villa, A; Kowalczyk, K; Jersie-Christensen, Rr; Bertalot, G; Confalonieri, S; Brunak, S; Jensen, Lj; Cavallaro, U; Olsen, Jv. - In: CELL REPORTS. - ISSN 2211-1247. - 18:13(2017), pp. 3242-3256. [10.1016/j.celrep.2017.03.015]

Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer

Bertalot G;
2017-01-01

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.
2017
13
Francavilla, C; Lupia, M; Tsafou, K; Villa, A; Kowalczyk, K; Jersie-Christensen, Rr; Bertalot, G; Confalonieri, S; Brunak, S; Jensen, Lj; Cavallaro, U; Olsen, Jv
Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer / Francavilla, C; Lupia, M; Tsafou, K; Villa, A; Kowalczyk, K; Jersie-Christensen, Rr; Bertalot, G; Confalonieri, S; Brunak, S; Jensen, Lj; Cavallaro, U; Olsen, Jv. - In: CELL REPORTS. - ISSN 2211-1247. - 18:13(2017), pp. 3242-3256. [10.1016/j.celrep.2017.03.015]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/361785
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