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J Proteome Res. 2018 Jun 1;17(6):2216-2225. doi: 10.1021/acs.jproteome.8b00180. Epub 2018 May 18.

Multiproteomic and Transcriptomic Analysis of Oncogenic β-Catenin Molecular Networks.

Author information

1
School of Biological Sciences , University of Southampton , Southampton SO17 1BJ , United Kingdom.
2
School of Medicine , Case Western Reserve University , Cleveland , Ohio 44106 , United States.

Abstract

The dysregulation of Wnt signaling is a frequent occurrence in many different cancers. Oncogenic mutations of CTNNB1/β-catenin, the key nuclear effector of canonical Wnt signaling, lead to the accumulation and stabilization of β-catenin protein with diverse effects in cancer cells. Although the transcriptional response to Wnt/β-catenin signaling activation has been widely studied, an integrated understanding of the effects of oncogenic β-catenin on molecular networks is lacking. We used affinity-purification mass spectrometry (AP-MS), label-free liquid chromatography-tandem mass spectrometry, and RNA-Seq to compare protein-protein interactions, protein expression, and gene expression in colorectal cancer cells expressing mutant (oncogenic) or wild-type β-catenin. We generate an integrated molecular network and use it to identify novel protein modules that are associated with mutant or wild-type β-catenin. We identify a DNA methyltransferase I associated subnetwork that is enriched in cells with mutant β-catenin and a subnetwork enriched in wild-type cells associated with the CDKN2A tumor suppressor, linking these processes to the transformation of colorectal cancer cells through oncogenic β-catenin signaling. In summary, multiomics analysis of a defined colorectal cancer cell model provides a significantly more comprehensive identification of functional molecular networks associated with oncogenic β-catenin signaling.

KEYWORDS:

DNA methyltransferase I; Wnt signaling; multiomics integration; oncogenic mutations; protein−protein interaction network; β-catenin

PMID:
29747501
DOI:
10.1021/acs.jproteome.8b00180
[Indexed for MEDLINE]

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