期刊
CELL REPORTS
卷 20, 期 9, 页码 2201-2214出版社
CELL PRESS
DOI: 10.1016/j.celrep.2017.08.010
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资金
- Wellcome Trust [098051]
- European Research Council under the European Union's Seventh Framework Programme (FP7)/ERC synergy grant [319661 COMBATCANCER]
- Merck KGaA, Darmstadt, Germany
- Cancer Research UK [13031] Funding Source: researchfish
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.
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