PXD065164

PXD065164 is an original dataset announced via ProteomeXchange.

Title	Intraductal xenografts reveal LOX inhibitor PXS-5505 as a translatable targeting strategy for lobular carcinoma exploiting a unique vulnerability
Description	Fifteen percent of breast cancers are invasive lobular carcinomas (ILCs), a specific histological subtype. Although ILCs have distinct clinicopathological features and pathognomonic CDH1 loss, no specific therapies exist because ILCs are underrepresented in clinical trials and preclinical models are lacking. We developed intraductal ILC xenograft models to test the hypothesis that the pan-LOX inhibitor (LOXi), PXS-5505, used in patients with myelofibrosis can be repurposed to target ILC-specific matrix dependency. LOXi blocks ILC progression in clinically relevant settings and alters collagen fiber organisation and cell matrix composition. In vitro screens identify ITGAV and ITGB5 loss as synthetic lethal in cells with CDH1 loss. Consistent with ILC specific dependency on ITG-mediated matrix interactions, expression of downstream factors CCN1, MYC, NFKB and AP-1 are increased in ILCs and downregulated by LOXi. We identify collagen fibre density and alignment, and MYC/AP-1 signatures as translatable endpoints of LOXi activity enabling needed clinical trials on ILCs.
HostingRepository	PRIDE
AnnounceDate	2026-01-29
AnnouncementXML	Submission_2026-01-29_12:32:39.645.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Graeme Benstead-Hume
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Ascend

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-18 09:09:27	ID requested
⏵ 1	2026-01-29 12:32:40	announced

Dataset with its publication pending

submitter keyword: PXS-5505, lobular carcinoma,LOX inhibitor

Jyoti Choudhary
contact affiliation	Functional Proteomics, ICR
contact email	jyoti.choudhary@icr.ac.uk
lab head
Graeme Benstead-Hume
contact affiliation	ICR
contact email	ghume@icr.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/2026/01/PXD065164

PRIDE project URI

• PRIDE
  1. PXD065164
     1. Label: PRIDE project
     2. Name: Intraductal xenografts reveal LOX inhibitor PXS-5505 as a translatable targeting strategy for lobular carcinoma exploiting a unique vulnerability