Genomic Determinants of Protein Abundance Variation in Colorectal Cancer Cells

Genomic Determinants of Protein Abundance Variation in Colorectal Cancer Cells

Roumeliotis, Theodoros I. (Wellcome Trust Sanger Institute)
Williams, Steven P. (Wellcome Trust Sanger Institute)
Gonçalves, Emanuel (European Molecular Biology Laboratory)
Alsinet, Clara (Wellcome Trust Sanger Institute)
Del Castillo Velasco-Herrera, Martin (Wellcome Trust Sanger Institute)
Aben, N.N. (Netherlands Cancer Institute)
Zamanzad Ghavidel, Fatemeh (European Molecular Biology Laboratory)
Michaut, Magali (Netherlands Cancer Institute)
Schubert, Michael (European Molecular Biology Laboratory)
Price, Stacey (Wellcome Trust Sanger Institute)
Wessels, L.F.A. (TU Delft Pattern Recognition and Bioinformatics; Netherlands Cancer Institute)

2017

Assessing the impact of genomic alterations on protein networks is fundamental in identifying the mechanisms that shape cancer heterogeneity. We have used isobaric labeling to characterize the proteomic landscapes of 50 colorectal cancer cell lines and to decipher the functional consequences of somatic genomic variants. The robust quantification of over 9,000 proteins and 11,000 phosphopeptides on average enabled the de novo construction of a functional protein correlation network, which ultimately exposed the collateral effects of mutations on protein complexes. CRISPR-cas9 deletion of key chromatin modifiers confirmed that the consequences of genomic alterations can propagate through protein interactions in a transcript-independent manner. Lastly, we leveraged the quantified proteome to perform unsupervised classification of the cell lines and to build predictive models of drug response in colorectal cancer. Overall, we provide a deep integrative view of the functional network and the molecular structure underlying the heterogeneity of colorectal cancer cells.

cell lines
colorectal cancer
CRISPR/cas9
drug response
mutations
networks
phosphorylation
protein complexes
proteomics
TMT

http://resolver.tudelft.nl/uuid:7bc71cc8-2ffc-45ea-88d2-e002e9dec8df

https://doi.org/10.1016/j.celrep.2017.08.010

2211-1247

Cell Reports, 20 (9), 2201-2214

Institutional Repository

journal article

© 2017 Theodoros I. Roumeliotis, Steven P. Williams, Emanuel Gonçalves, Clara Alsinet, Martin Del Castillo Velasco-Herrera, N.N. Aben, Fatemeh Zamanzad Ghavidel, Magali Michaut, Michael Schubert, Stacey Price, L.F.A. Wessels, More Authors