期刊
CELL REPORTS
卷 18, 期 13, 页码 3242-3256出版社
CELL PRESS
DOI: 10.1016/j.celrep.2017.03.015
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资金
- Novo Nordisk Foundation [NNF14CC0001]
- European Union's Horizon research and innovation programme [686547]
- Danish Research Council
- Danish Cancer Society [R90-A5844KBVU]
- Lundbeckfonden [R191-2015-703]
- Marie Curie IEF(FP7-PEOPLE-IEF [252594]
- EMBO Long-Term (ALTF) [746-2009]
- Wellcome Trust [107636/Z/15/Z]
- Associazione Italiana Ricerca sul Cancro (AIRC) [IG-1462]
- Association for International Cancer Research (AICR) [10-0091]
- AIRC [1462, 12378]
- Association for International Cancer Research (AICR [10-0091]
- Fondazione Umberto Veronesi postdoctoral fellowships
- Fondazione Istituto Europeo di Oncologia postdoctoral fellowships
- Lundbeck Foundation [R191-2015-703] Funding Source: researchfish
- Novo Nordisk Foundation Center for Protein Research [PI Jesper Velgaard Olsen, PI Søren Brunak, PI Lars Juhl Jensen] Funding Source: researchfish
- The Danish Cancer Society [R90-A5844] Funding Source: researchfish
- Wellcome Trust [107636/Z/15/Z] Funding Source: Wellcome Trust
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.
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