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Cell. 2020 Jan 23;180(2):387-402.e16. doi: 10.1016/j.cell.2019.12.023.

Quantitative Proteomics of the Cancer Cell Line Encyclopedia.

Author information

1
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: david_nusinow@hms.harvard.edu.
2
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
3
Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
4
Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
5
Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
6
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: steven_gygi@hms.harvard.edu.

Abstract

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.

KEYWORDS:

CCLE; MSI; RNA/Protein correlation; TMT; cancer cell lines; microsatellite instability; protein expression; quantitative proteomics; systems biology

PMID:
31978347
DOI:
10.1016/j.cell.2019.12.023

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