PXD050634-2

PXD050634 is an original dataset announced via ProteomeXchange.

Title	ONECUT2 acts a lineage plasticity driver
Description	Androgen receptor- (AR-) indifference is a mechanism of resistance to hormonal therapy in prostate cancer (PC). Here we demonstrate that ONECUT2 (OC2) activates resistance through multiple drivers associated with adenocarcinoma, stem-like and neuroendocrine (NE) variants. Direct OC2 gene targets include the glucocorticoid receptor (GR; NR3C1) and the NE splicing factor SRRM4, which are key drivers of lineage plasticity. Thus, OC2, despite its previously described NEPC driver function, can indirectly activate a portion of the AR cistrome through epigenetic activation of GR. Mechanisms by which OC2 regulates gene expression include promoter binding, enhancement of genome-wide chromatin accessibility, and super-enhancer reprogramming. Pharmacologic inhibition of OC2 suppresses lineage plasticity reprogramming induced by the AR signaling inhibitor enzalutamide. These results demonstrate that OC2 activation promotes a range of drug resistance mechanisms associated with treatment-emergent lineage variation in PC and support enhanced efforts to therapeutically target OC2 as a means of suppressing treatment-resistant disease.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:54:11.338.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wei Yang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-14 18:26:34	ID requested
1	2024-08-10 12:03:26	announced
⏵ 2	2024-10-22 06:54:14	announced	2024-10-22: Updated project metadata.

Qian C, Yang Q, Rotinen M, Huang R, Kim H, Gallent B, Yan Y, Cadaneanu RM, Zhang B, Kaochar S, Freedland SJ, Posadas EM, Ellis L, Di Vizio D, Morrissey C, Nelson PS, Brady L, Murali R, Campbell MJ, Yang W, Knudsen BS, Mostaghel EA, Ye H, Garraway IP, You S, Freeman MR, ONECUT2 acts as a lineage plasticity driver in adenocarcinoma as well as neuroendocrine variants of prostate cancer. Nucleic Acids Res, 52(13):7740-7760(2024) [pubmed]

10.1093/nar/gkae547;

submitter keyword: ONECUT2, prostate cancer, interactome, LC-MS/MS

Wei Yang
contact affiliation	Department of Pathology and Cancer Center, Stony Brook University, Stony Brook, NY 11794
contact email	omician@gmail.com
lab head
Wei Yang
contact affiliation	Stony Brook University
contact email	omician@gmail.com
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/2024/08/PXD050634

PRIDE project URI

• PRIDE
  1. PXD050634
     1. Label: PRIDE project
     2. Name: ONECUT2 acts a lineage plasticity driver