PXD014632

PXD014632 is an original dataset announced via ProteomeXchange.

Title	Deep proteomic analysis of Dnmt1 mutant/hypomorphic colorectal cancer cells reveals dys-regulation of Epithelial-Mesenchymal Transition and subcellular re-localization of Beta-Catenin
Description	DNA methyltransferase I plays the central role in maintenance of CpG DNA methylation patterns across the genome and alteration of CpG methylation patterns is a frequent and significant occurrence across many cancers. Cancer cells carrying hypomorphic alleles of Dnmt1 have become important tools for understanding Dnmt1 function and CpG methylation. In this study, we analyse colorectal cancer cells with a homozygous deletion of exons 3 to 5 of Dnmt1, resulting in reduced Dnmt1 activity. Although this cell model has been widely used to study the epigenome, the effects of the Dnmt1 hypomorph on cell signalling pathways and the wider proteome are largely unknown. In this study, we perform the first quantitative proteomic analysis of this important cell model and identify multiple signalling pathways and processes that are significantly dysregulated in the hypomorph cells. In Dnmt1 hypomorph cells, we observed a clear and unexpected signature of increased Epithelial-to-Mesenchymal transition (EMT) markers as well as reduced expression and sub-cellular re-localization of Beta-Catenin. Expression of wild-type Dnmt1 in hypomorph cells or knock-down of wild-type Dnmt1 did not recapitulate or rescue the observed protein profiles in Dnmt1 hypomorph cells suggesting that hypomorphic Dnmt1 causes changes not solely attributable to Dnmt1 protein levels. In summary we present the first comprehensive proteomic analysis of the widely studied Dnmt1 hypomorph colorectal cancer cells and identify redistribution of Dnmt1 and its interaction partner Beta-Catenin
HostingRepository	PRIDE
AnnounceDate	2021-09-08
AnnouncementXML	Submission_2021-09-08_14:52:22.045.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD014632
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Rob Ewing
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Carbamidomethyl
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-16 05:25:41	ID requested
⏵ 1	2021-09-08 14:52:22	announced

Bowler EH, Smith-Vidal A, Lester A, Bell J, Wang Z, Bell CG, Wang Y, Divecha N, Skipp PJ, Ewing RM, Deep proteomic analysis of Dnmt1 mutant/hypomorphic colorectal cancer cells reveals dysregulation of epithelial-mesenchymal transition and subcellular re-localization of Beta-Catenin. Epigenetics, 15(1-2):107-121(2020) [pubmed]

submitter keyword: Dnmt1

methltransferase

HCT116

colorectal cancer

Rob Ewing
contact affiliation	University of Southampton
contact email	rob.ewing@soton.ac.uk
lab head
Rob Ewing
contact affiliation	Univ Southampton
contact email	rob.ewing@soton.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014632
     1. Label: PRIDE project
     2. Name: Deep proteomic analysis of Dnmt1 mutant/hypomorphic colorectal cancer cells reveals dys-regulation of Epithelial-Mesenchymal Transition and subcellular re-localization of Beta-Catenin