Deep proteomic analysis of Dnmt1 mutant/hypomorphic colorectal cancer cells reveals dysregulation of epithelial-mesenchymal transition and subcellular re-localization of Beta-Catenin.

摘要: DNA methyltransferase I plays the central role in maintenance of CpG methylation patterns across genome and alteration is a frequent significant occurrence many cancers. Cancer cells carrying hypomorphic alleles Dnmt1 have become important tools for understanding function methylation. In this study, we analyse colorectal cancer with homozygous deletion exons 3 to 5 Dnmt1, resulting reduced activity. Although cell model has been widely used study epigenome, effects hypomorph on signalling pathways wider proteome are largely unknown. perform first quantitative proteomic analysis identify multiple processes that significantly dysregulated cells. cells, observed clear unexpected signature increased Epithelial-to-Mesenchymal transition (EMT) markers as well expression sub-cellular re-localization Beta-Catenin. Expression wild-type or knock-down did not recapitulate rescue protein profiles suggesting causes changes solely attributable levels. summary, present comprehensive studied redistribution its interaction partner