Daniel Liebler
Faculty Member
Last active: 2/15/2016

Proteomic consequences of a single gene mutation in a colorectal cancer model.

Halvey PJ, Zhang B, Coffey RJ, Liebler DC, Slebos RJ
J Proteome Res. 2012 11 (2): 1184-95

PMID: 22103262 · PMCID: PMC3271737 · DOI:10.1021/pr2009109

The proteomic effects of specific cancer-related mutations have not been well characterized. In colorectal cancer (CRC), a relatively small number of mutations in key signaling pathways appear to drive tumorigenesis. Mutations in adenomatous polyposis coli (APC), a negative regulator of Wnt signaling, occur in up to 60% of CRC tumors. Here we examine the proteomic consequences of a single gene mutation by using an isogenic CRC cell culture model in which wildtype APC expression has been ectopically restored. Using LC-MS/MS label free shotgun proteomics, over 5000 proteins were identified in SW480Null (mutant APC) and SW480APC (APC restored). We observed 155 significantly differentially expressed proteins between the two cell lines, with 26 proteins showing opposite expression trends relative to gene expression measurements. Protein changes corresponded to previously characterized features of the APCNull phenotype: loss of cell adhesion proteins, increase in cell cycle regulators, alteration in Wnt signaling related proteins, and redistribution of β-catenin. Increased expression of RNA processing and isoprenoid biosynthetic proteins occurred in SW480Null cells. Therefore, shotgun proteomics reveals proteomic differences associated with a single gene change, including many novel differences that fall outside known target pathways.

MeSH Terms (14)

Cell Line, Tumor Cluster Analysis Colorectal Neoplasms Cytoplasm Genes, APC Humans Models, Genetic Mutation Peptide Mapping Proteome Proteomics Reproducibility of Results Signal Transduction Tandem Mass Spectrometry

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