TY - JOUR
T1 - Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer
AU - Francavilla, Chiara
AU - Lupia, Michela
AU - Tsafou, Kalliopi P
AU - Villa, Alessandra
AU - Kowalczyk, Katarzyna
AU - Rakownikow Jersie-Christensen, Rosa
AU - Bertalot, Giovanni
AU - Confalonieri, Stefano
AU - Brunak, Søren
AU - Jensen, Lars J
AU - Cavallaro, Ugo
AU - Olsen, Jesper V
PY - 2017/3/28
Y1 - 2017/3/28
N2 - 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.
AB - 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.
U2 - 10.1016/j.celrep.2017.03.015
DO - 10.1016/j.celrep.2017.03.015
M3 - Article
VL - 18
SP - 3242
EP - 3256
JO - Cell Reports
JF - Cell Reports
IS - 13
ER -