PXD065374

PXD065374 is an original dataset announced via ProteomeXchange.

Title	GOT1 inhibition induces extracellular matrix remodeling in pancreatic cancer
Description	Pancreatic ductal adenocarcinoma (PDAC) cells rely on glutamine to sustain their survival and growth in their stiff, hypoxic tumour microenvironment (TME). Inhibiting the glutamate oxaloacetate transaminase 1 (GOT1) enzyme is a promising strategy to target glutamine metabolism and impair PDAC cell function. However, how the cellular and extracellular elements of the TME influence cell responses to GOT1 inhibition remains unclear. Using tumour tissue engineering, we built a 3D model to recreate PDAC tissues ‘on a dish’ and the metabolic interactions of the TME. Stromal cells remodelled the extracellular matrix and upregulated different metabolic programs, including glutamine metabolism, oxidative phosphorylation, and central carbon metabolism. Cell responses to treatment with a GOT1 inhibitor were modulated by the matrix composition, decreasing cell viability and proliferation only under PDAC-like conditions. GOT1 inhibition altered the matrix organisation and composition, promoting the upregulation of different collagen isotypes and fibronectin. In addition, GOT1 inhibition effectively targeted patient-derived cells and modulated their glutamine metabolism, while no synergistic effect with cytotoxic drugs was observed. Our findings shed light on the metabolic cross-talk within the pancreatic TME and show that stromal elements dictate the effects of metabolism-targeting treatments.
HostingRepository	PRIDE
AnnounceDate	2026-01-12
AnnouncementXML	Submission_2026-01-11_20:57:42.871.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joel Steele
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-23 23:44:59	ID requested
⏵ 1	2026-01-11 20:57:43	announced

Dataset with its publication pending

submitter keyword: None

Rodrigo Curvello
contact affiliation	Daniela Loessner, daniela.loessner@monash.edu, Department of Chemical and Biological Engineering, Faculty of Engineering, Monash University, Clayton, Australia
contact email	rodrigo.curvello@monash.edu
lab head
Joel Steele
contact affiliation	Monash
contact email	joel.steele@monash.edu
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/PXD065374

PRIDE project URI

• PRIDE
  1. PXD065374
     1. Label: PRIDE project
     2. Name: GOT1 inhibition induces extracellular matrix remodeling in pancreatic cancer