PXD042750

PXD042750 is an original dataset announced via ProteomeXchange.

Title	Exploiting TGF-β-mediated Stromal Programming in Homologous Recombination-Deficient Pancreatic Cancer
Description	The tumor microenvironment (TME) actively contributes to pancreatic ductal adenocarcinoma (PDAC) pathogenesis via a dynamic bidirectional tumor–stroma dialog. Here, we show that homologous recombination-defective (HRD) neoplastic epithelium reprograms its TME in a genotype-specific manner to promote cancer aggressiveness. Autochthonous mouse models, co-culture systems, and human PDAC specimens revealed that tumoral ATM serine/threonine kinase status impacts cancer-associated fibroblast fate towards αSMA+ myofibroblastic (myCAF) differentiation, while P53 operates mostly tumor cell intrinsic. Vice versa, myCAFs foster cancer aggressiveness and specific chemoresistance patterns. Secretomics, proteomics, and in vitro approaches uncovered a greater TGF-β1 release in ATM-deficient cells associated with an enhanced reactive oxygen species/actomyosin-mediated mechanism. Pharmacological interference with TGF-β signaling reverts myofibroblast differentiation, chemoresistance, and tumor promotion in various ATM-deficient PDAC models. Overall, our findings demonstrate specific TME reprogramming by HRD PDACs towards a cancer-promoting fate, and their eligibility for combinatorial therapies targeting intrinsic vulnerabilities and extrinsic tumor–stroma oncogenic crosstalks.
HostingRepository	PRIDE
AnnounceDate	2026-04-27
AnnouncementXML	Submission_2026-04-27_03:16:51.383.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christina Ludwig
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-05 22:55:33	ID requested
⏵ 1	2026-04-27 03:16:51	announced

Dataset with its publication pending

submitter keyword: P53, ATM, tumor–stroma crosstalk,Pancreatic ductal adenocarcinoma, personalized medicine, cancer-associated fibroblasts, tumor microenvironment

Christina Ludwig
contact affiliation	Bavarian Center for Biomolecular Mass Spectrometry (BayBioMS) School of Life Sciences Technical University Munich (TUM) Gregor-Mendel-Straße 4 85354 Freising GERMANY Bavarian Center for Biomolecular Mass Spectrometry Technische Universität München Gregor-Mendel-Straße 4 85354 Freising DEUTSCHLAND / GERMANY
contact email	tina.ludwig@tum.de
lab head
Christina Ludwig
contact affiliation	TU Munich
contact email	tina.ludwig@tum.de
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/2026/04/PXD042750

PRIDE project URI

• PRIDE
  1. PXD042750
     1. Label: PRIDE project
     2. Name: Exploiting TGF-β-mediated Stromal Programming in Homologous Recombination-Deficient Pancreatic Cancer