Quantitative Proteomics of the Cancer Cell Line Encyclopedia

• Published in: Cell Vol. 180; no. 2; pp. 387 - 402.e16
• Main Authors: Nusinow, David P., Szpyt, John, Ghandi, Mahmoud, Rose, Christopher M., McDonald, E. Robert, Kalocsay, Marian, Jané-Valbuena, Judit, Gelfand, Ellen, Schweppe, Devin K., Jedrychowski, Mark, Golji, Javad, Porter, Dale A., Rejtar, Tomas, Wang, Y. Karen, Kryukov, Gregory V., Stegmeier, Frank, Erickson, Brian K., Garraway, Levi A., Sellers, William R., Gygi, Steven P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.01.2020
• Subjects: cancer cell lines; CCLE; Cell Line, Tumor; cell lines; DNA; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic - genetics; genes; Humans; mass spectrometry; Mass Spectrometry - methods; Microsatellite Instability; microsatellite repeats; monitoring; MSI; mutation; Mutation - genetics; neoplasm cells; neoplasms; Neoplasms - metabolism; protein expression; proteins; proteome; Proteome - metabolism; proteomics; Proteomics - methods; quantitative proteomics; RNA; RNA/Protein correlation; systems biology; TMT; translation (genetics); systems biology; microsatellite instability; MSI; CCLE; TMT; cancer cell lines; protein expression; quantitative proteomics; RNA/Protein correlation
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2019.12.023

Proteins are essential agents of biological processes. To date, large-scale profiling of cell line collections including the Cancer Cell Line Encyclopedia (CCLE) has focused primarily on genetic information whereas deep interrogation of the proteome has remained out of reach. Here, we expand the CCLE through quantitative profiling of thousands of proteins by mass spectrometry across 375 cell lines from diverse lineages to reveal information undiscovered by DNA and RNA methods. We observe unexpected correlations within and between pathways that are largely absent from RNA. An analysis of microsatellite instable (MSI) cell lines reveals the dysregulation of specific protein complexes associated with surveillance of mutation and translation. These and other protein complexes were associated with sensitivity to knockdown of several different genes. These data in conjunction with the wider CCLE are a broad resource to explore cellular behavior and facilitate cancer research. [Display omitted] •Quantified the proteomes of 375 cell lines from diverse lineages in the CCLE•Correlated expression of proteins across many pathways•Downregulation of multiple protein complexes in microsatellite instability•Protein complexes associated with sensitivity to gene knockdown and mutation Quantitative proteomes of 375 cancer cell lines for the Cancer Cell Line Encyclopedia (CCLE) reveal correlated protein expression between multiple pathways and complexes as well as associations between protein complexes and genetic features including microsatellite instability, individual gene mutations, and sensitivity to gene knockdowns.