PXD005494

PXD005494 is an original dataset announced via ProteomeXchange.

Title	The chromatin assembly factor complex 1 (CAF1) and 5-Azacytidine (5-AzaC) affect cell motility in Src-transformed human epithelial cells
Description	Tumor invasion into surrounding stromal tissue is a hallmark of high-grade, metastatic cancers. Oncogenic transformation of human epithelial cells in culture can be triggered by activation of v-Src kinase, resulting in increased cell motility, invasiveness and tumorigenicity and provides a valuable model for studying how changes in gene expression cause cancer phenotypes. Here, we show that epithelial cells transformed by activated Src show increased levels of DNA methylation and that the methylation inhibitor, 5-AzaC, potently blocks the increased cell motility and invasiveness induced by Src activation. A proteomic screen for chromatin regulators acting downstream of activated Src identified the replication-dependent histone chaperone CAF1 as an important factor for Src-mediated increased cell motility and invasion. We show Src causes a 5-AzaC-sensitive decrease in both mRNA and protein levels of the p150 (CHAF1A) and p60 (CHAF1B), subunits of CAF1. Depletion of CAF1 in untransformed epithelial cells using siRNA was sufficient to recapitulate the increased motility and invasive phenotypes characteristic of transformed cells without activation of Src. Maintaining high levels of CAF1 by exogenous expression suppressed the increased cell motility and invasiveness phenotypes when Src was activated. These data identify a critical role of CAF1 in the dysregulation of cell invasion and motility phenotypes seen in transformed cells and also highlight an important role for epigenetic remodeling through DNA methylation for Src-mediated induction of cancer phenotypes.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:34:18.293.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tony Ly
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-12-03 08:18:04	ID requested
1	2016-12-20 07:04:04	announced
2	2017-06-06 08:26:16	announced	Updated publication reference for PubMed record(s): 27872192.
⏵ 3	2024-10-22 04:34:19	announced	2024-10-22: Updated project metadata.

Endo A, Ly T, Pippa R, Bensaddek D, Nicolas A, Lamond AI, The Chromatin Assembly Factor Complex 1 (CAF1) and 5-Azacytidine (5-AzaC) Affect Cell Motility in Src-transformed Human Epithelial Cells. J Biol Chem, 292(1):172-184(2017) [pubmed]

10.1074/jbc.M116.751024;

curator keyword: Biological

submitter keyword: epigenetics,proteomics, invasion

Angus I. Lamond
contact affiliation	Centre for Gene Regulation and Expression University of Dundee
contact email	ailamond@dundee.ac.uk
lab head
Tony Ly
contact affiliation	University of Edinburgh
contact email	tly@ed.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2016/12/PXD005494

PRIDE project URI

• PRIDE
  1. PXD005494
     1. Label: PRIDE project
     2. Name: The chromatin assembly factor complex 1 (CAF1) and 5-Azacytidine (5-AzaC) affect cell motility in Src-transformed human epithelial cells