PXD050634-2
PXD050634 is an original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
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; |
Keyword List
submitter keyword: ONECUT2, prostate cancer, interactome, LC-MS/MS |
Contact List
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 |
Full Dataset Link List
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 |
Repository Record List
[ + ]