PXD058236-1

PXD058236 is an original dataset announced via ProteomeXchange.

Title	Shifted assembly and function of mSWI/SNF family subcomplexes underlie targetable dependencies in endometriod carcinomas
Description	The mammalian SWI/SNF (mSWI/SNF) family of chromatin remodelers govern cell type-specific chromatin accessibility and gene expression and assemble as three distinct complexes: canonical BAF (cBAF), Polybromo-associated BAF (PBAF), and non-canonical BAF (ncBAF). ARID1A and ARID1B are paralog subunits that specifically nucleate the assembly of cBAF complexes and are frequently dual deleted in highly aggressive differentiated endometrial carcinomas (DECs). Here, in cellular models and primary human tumors, we find that ARID1A/B-mediated cBAF loss results in increased ncBAF and PBAF biochemical abundance and function genome-wide to maintain the DEC oncogenic signature. Further, treatment of ARID1A/1B-mutant cell lines and PDX models in vivo with a clinical-grade SMARCA4/2 ATPase inhibitor, FHD-286, markedly attenuates cell proliferation and tumor growth, and synergizes with carboplatin-based chemotherapy. Taken together, these findings reveal the oncogenic contributions of shifted of mSWI/SNF family complex abundance and chromatin-level gene regulatory functions and suggest therapeutic utility of mSWI/SNF complex small molecule inhibitors in dedifferentiated endometrial carcinoma and other cBAF-disrupted cancer types.
HostingRepository	PRIDE
AnnounceDate	2025-08-07
AnnouncementXML	Submission_2025-08-07_12:36:14.962.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD058236
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Alexander Ying
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-25 07:15:21	ID requested
⏵ 1	2025-08-07 12:36:15	announced

10.6019/PXD058236;

submitter keyword: VOA1066, Dedifferentiated, cBAF, ncBAF, Endometrical Carcinoma, UCEC,BAF, AN3CA, Endometriod Carcinoma, PBAF

Cigall Kadoch
contact affiliation	Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA
contact email	Cigall_Kadoch@dfci.harvard.edu
lab head
Alexander Ying
contact affiliation	Broad Institute Dana-Farber Cancer Institute Harvard Medical School
contact email	yingalex@broadinstitute.org
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/PXD058236

PRIDE project URI

• PRIDE
  1. PXD058236
     1. Label: PRIDE project
     2. Name: Shifted assembly and function of mSWI/SNF family subcomplexes underlie targetable dependencies in endometriod carcinomas