Multiproteomic and Transcriptomic Analysis of Oncogenic β-Catenin Molecular Networks

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinogenesis* / chemistry
  • Carcinogenesis* / genetics
  • Colorectal Neoplasms / pathology*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • DNA (Cytosine-5-)-Methyltransferase 1 / metabolism
  • Gene Expression Profiling*
  • Humans
  • Proteomics / methods*
  • Wnt Signaling Pathway
  • beta Catenin / genetics
  • beta Catenin / metabolism*


  • CDKN2A protein, human
  • CTNNB1 protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • beta Catenin
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNMT1 protein, human