PXD063452

PXD063452 is an original dataset announced via ProteomeXchange.

Title	Matrix stiffness drives alterations in aldehyde metabolism, inducing DNA damage and transformation
Description	Microenvironmental stiffness regulates fundamental aspects of cell behaviour, including proliferation, differentiation and metabolism, many of which are implicated in cancer initiation and progression. In the mammary gland, extracellular matrix (ECM) stiffness, associated with high mammographic density, is linked to increased breast cancer incidence. However, a mechanistic link between increased ECM stiffness and the genomic damage required for transforming mutations remains unclear. Here we show that ECM stiffness induces changes in mammary epithelial cell (MEC) metabolism which drive DNA damage. Using a mechanically tunable 3D-culture model, we demonstrate that transcriptional changes in response to increased ECM stiffness impair the ability of MECs to remove reactive aldehydes. Downregulation of multiple aldehyde dehydrogenase isoforms in MECs within a stiffer 3D ECM leads to higher levels of reactive aldehydes, resulting in genomic damage and transformation. Together, these results provide a mechanistic link between increased ECM stiffness and the genomic damage required for breast cancer initiation.
HostingRepository	PRIDE
AnnounceDate	2025-09-04
AnnouncementXML	Submission_2025-09-04_01:42:33.760.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrew Gilmore
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-29 08:21:38	ID requested
⏵ 1	2025-09-04 01:42:34	announced

10.1038/S41598-025-12880-0;

submitter keyword: ECM, mechanosignalling,Mammary epithelia

Andrew Gilmore
contact affiliation	Manchester Cell Matrix Centre | Division of Cancer Sciences | School of Medical Sciences | Faculty of Biology, Medicine and Health The University of Manchester | Michael Smith Building | Oxford Road | Manchester M13 9PT
contact email	andrew.gilmore@manchester.ac.uk
lab head
Andrew Gilmore
contact affiliation	Wellcome Trust Centre for Cell/Matrix Research Division of Cancer Sciences School of Medical Sciences Faculty of Biology, Medicine and Health The University of Manchester
contact email	andrew.gilmore@manchester.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/2025/09/PXD063452

PRIDE project URI

• PRIDE
  1. PXD063452
     1. Label: PRIDE project
     2. Name: Matrix stiffness drives alterations in aldehyde metabolism, inducing DNA damage and transformation