Genomic Determinants of Protein Abundance Variation in Colorectal Cancer Cells

Cell Rep. 2017 Aug 29;20(9):2201-2214. doi: 10.1016/j.celrep.2017.08.010.


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.

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

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genome, Human*
  • Humans
  • Models, Biological
  • Mutation / genetics
  • Neoplasm Proteins / metabolism*
  • Phosphoproteins / metabolism
  • Protein Subunits / metabolism
  • Proteome / metabolism
  • Proteomics
  • Quantitative Trait Loci / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcription, Genetic / drug effects


  • Antineoplastic Agents
  • Neoplasm Proteins
  • Phosphoproteins
  • Protein Subunits
  • Proteome
  • RNA, Messenger