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Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer
- Source :
- Cell Reports, Vol 18, Iss 13, Pp 3242-3256 (2017), Francavilla, C, Lupia, M, Tsafou, K P, Villa, A, Kowalczyk, K, Rakownikow Jersie-Christensen, R, Bertalot, G, Confalonieri, S, Brunak, S, Jensen, L J, Cavallaro, U & Olsen, J V 2017, ' Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer ', Cell Reports, vol. 18, no. 13, pp. 3242-3256 . https://doi.org/10.1016/j.celrep.2017.03.015, Francavilla, C, Lupia, M, Tsafou, K, Villa, A, Kowalczyk, K, Rakownikow Jersie-Christensen, R, Bertalot, G, Confalonieri, S, Brunak, S, Jensen, L J, Cavallaro, U & Olsen, J V 2017, ' Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer ', Cell Reports, vol. 18, no. 13, pp. 3242-3256 . https://doi.org/10.1016/j.celrep.2017.03.015, Cell Reports
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Summary 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.<br />Graphical Abstract<br />Highlights • We analyze ex-vivo-cultured primary cells using phosphoproteomics • We investigate epithelial ovarian cancer (EOC) and healthy tissue • We uncover expression of cancer-specific proteins and kinase signatures • The kinase CDK7 phosphorylates POLR2A and regulates EOC cell proliferation<br />Francavilla et al. use mass-spectrometry-based phosphoproteomics as a powerful tool to reveal cancer signatures. They analyze changes in the proteome and phosphoproteome of primary cells derived from epithelial ovarian cancer (EOC) compared to healthy tissues and reveal a role for the kinase CDK7 in EOC cell proliferation.
- Subjects :
- Aalternative splicing
Proteomics
Resource
0301 basic medicine
quantitative proteomics
endocrine system diseases
POLR2A
Quantitative proteomics
ovarian cancer
phosphoproteomics
CDK7
POLR2
EOC
fimbriae
OSE
THZ1
Carcinoma, Ovarian Epithelial
Biology
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
alternative splicing
0302 clinical medicine
Tumor Cells, Cultured
medicine
Humans
Neoplasms, Glandular and Epithelial
lcsh:QH301-705.5
Ovarian Neoplasms
Cell growth
Kinase
Phosphoproteomics
Cancer
Epithelial Cells
Phosphoproteins
medicine.disease
female genital diseases and pregnancy complications
Neoplasm Proteins
3. Good health
030104 developmental biology
lcsh:Biology (General)
Cell culture
030220 oncology & carcinogenesis
Spliceosomes
Cancer research
Female
Cyclin-dependent kinase 7
Ovarian cancer
Protein Kinases
Subjects
Details
- ISSN :
- 22111247
- Volume :
- 18
- Issue :
- 13
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....8b9f7e9f7c9becd7382a0a6cac835fac
- Full Text :
- https://doi.org/10.1016/j.celrep.2017.03.015