Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer
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-s...
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doaj-b22efed567f248cf8c6df37c936433392020-11-24T21:54:08ZengElsevierCell Reports2211-12472017-03-0118133242325610.1016/j.celrep.2017.03.015Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian CancerChiara Francavilla0Michela Lupia1Kalliopi Tsafou2Alessandra Villa3Katarzyna Kowalczyk4Rosa Rakownikow Jersie-Christensen5Giovanni Bertalot6Stefano Confalonieri7Søren Brunak8Lars J. Jensen9Ugo Cavallaro10Jesper V. Olsen11Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, DenmarkUnit of Gynecological Oncology Research, Program of Gynecological Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, ItalyDisease Systems Biology Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, DenmarkUnit of Gynecological Oncology Research, Program of Gynecological Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, ItalyDivision of Molecular and Cellular Functions, School of Biological Sciences, Faculty of Biology, Medicine and Health, the University of Manchester, Manchester M13 9PL, UKProteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, DenmarkProgram of Molecular Medicine, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, ItalyProgram of Molecular Medicine, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, ItalyDisease Systems Biology Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, DenmarkDisease Systems Biology Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, DenmarkUnit of Gynecological Oncology Research, Program of Gynecological Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, ItalyProteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, DenmarkOur 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.http://www.sciencedirect.com/science/article/pii/S2211124717303327ovarian cancerquantitative proteomicsphosphoproteomicsCDK7POLR2Aalternative splicingEOCfimbriaeOSETHZ1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer Cell Reports ovarian cancer quantitative proteomics phosphoproteomics CDK7 POLR2A alternative splicing EOC fimbriae OSE THZ1 |
author_facet |
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 |
author_sort |
Chiara Francavilla |
title |
Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer |
title_short |
Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer |
title_full |
Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer |
title_fullStr |
Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer |
title_full_unstemmed |
Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer |
title_sort |
phosphoproteomics of primary cells reveals druggable kinase signatures in ovarian cancer |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2017-03-01 |
description |
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. |
topic |
ovarian cancer quantitative proteomics phosphoproteomics CDK7 POLR2A alternative splicing EOC fimbriae OSE THZ1 |
url |
http://www.sciencedirect.com/science/article/pii/S2211124717303327 |
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