PXD045980-1

PXD045980 is an original dataset announced via ProteomeXchange.

Title	HNF4G and FOXA1 are context-specific drivers of pancreatic cancer progression
Description	Despite recent advances in the treatment of pancreatic adenocarcinoma (PDAC), clinical outcome remains poor. Previous evidence linked the pioneer transcription factor FOXA1 as a mediator of new regulatory elements that drive tumour progression in models of late-stage disease. Given the critical role of FOXA1 as a pioneer factor for nuclear receptor (NR) transcription factors (TF) in breast and prostate cancer (Estrogen Receptor and Androgen Receptor), we hypothesised that FOXA1 might function with a NR in PDAC (1) (2). Using RIME, our unbiased approach for discovering endogenous protein complexes, we identified HNF4A and HNF4G as reproducible, FOXA1-associated proteins, a finding that was validated in clinical samples of PDAC. Using complex and diverse PDAC models, we show that gene transcription in the classical subtype of pancreatic cancer is regulated by FOXA1/GATA5/6 and HNF4G. We show that HNF4G drives primary disease, in part by recruiting the methyltransferase PRMT1 to regulatory regions. In primary tumour context, HNF4G is the dominant protein and the presence of HNF4G masks FOXA1 activity, resulting in FOXA1 being present, but functionally redundant in primary disease. During transition to metastasis however, HNF4G expression decreases, which unmasks FOXA1 activity, where it becomes transcriptionally active and a subsequent driver of metastasis. We provide new molecular insight into the key TFs in PDAC and the stage-specific activity of these proteins.
HostingRepository	PRIDE
AnnounceDate	2025-08-13
AnnouncementXML	Submission_2025-08-13_08:25:40.651.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Evangelia Papachristou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue
Instrument	Q Exactive HF; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-09 03:11:28	ID requested
⏵ 1	2025-08-13 08:25:41	announced

Dataset with its publication pending

submitter keyword: FOXA1, pancreatic adenocarcinoma, HNF4G, RIME

Jason S. Carroll
contact affiliation	Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
contact email	Jason.Carroll@cruk.cam.ac.uk
lab head
Evangelia Papachristou
contact affiliation	Senior Scientific Assistant
contact email	eva.papachristou@cruk.cam.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/2025/08/PXD045980

PRIDE project URI

• PRIDE
  1. PXD045980
     1. Label: PRIDE project
     2. Name: HNF4G and FOXA1 are context-specific drivers of pancreatic cancer progression