PXD047272

PXD047272 is an original dataset announced via ProteomeXchange.

Title	Spatiotemporal control of SMARCA5 by a MAPK-RUNX1 axis distinguishes mutant KRAS-driven pancreatic malignancy from tissue regeneration
Description	Acute pancreatitis-induced acinar-to-ductal metaplasia (ADM) involves global chromatin remodeling and contributes to normal tissue regeneration. Oncogenic KRAS hijacks this process to promote PDAC formation. Here we show that regeneration and KRASG12D-driven oncogenesis can be decoupled from tissue regeneration through a chromatin remodeler, SMARCA5. We show that SMARCA5 maintains KRASG12D-dependent chromatin accessibility at regions specifically required for malignancy, without affecting chromatin opening that occurs during normal regeneration. Without SMARCA5, regeneration can be restored in the presence of KRASG12D. Mechanistically, regeneration-related or malignancy-related chromatin remodeling activities occur in a time-sensitive manner. The activity of SMARCA5 is controlled spatiotemporally by transcription factor RUNX1, which only accumulates at sufficient levels with sustained MAPK signals. We further show that inhibition of the SMARCA5-containing NoRC complex specifically inhibits the growth of PDAC organoid but not that of normal tissue derived from patients.
HostingRepository	PRIDE
AnnounceDate	2025-08-23
AnnouncementXML	Submission_2025-08-23_05:59:57.738.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jing Han
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-27 06:26:59	ID requested
⏵ 1	2025-08-23 05:59:58	announced

Liu X, Guo Z, Han J, Peng B, Zhang B, Li H, Hu X, David CJ, Chen M, The PAF1 complex promotes 3' processing of pervasive transcripts. Cell Rep, 38(11):110519(2022) [pubmed]

10.1016/j.celrep.2022.110519;

submitter keyword: mousee SMARCA5 PDAC

Mo Chen
contact affiliation	State Key Laboratory of Molecular Oncology, School of Medicine, Tsinghua University, Beijing 100084, China
contact email	mochen@mail.tsinghua.edu.cn
lab head
Jing Han
contact affiliation	Tsinghua University
contact email	hanj18@mails.tsinghua.edu.cn
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/PXD047272

PRIDE project URI

• PRIDE
  1. PXD047272
     1. Label: PRIDE project
     2. Name: Spatiotemporal control of SMARCA5 by a MAPK-RUNX1 axis distinguishes mutant KRAS-driven pancreatic malignancy from tissue regeneration