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PXD050634

PXD050634 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleONECUT2 acts a lineage plasticity driver
DescriptionAndrogen 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:54:11.338.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterWei Yang
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-03-14 18:26:34ID requested
12024-08-10 12:03:26announced
22024-10-22 06:54:14announced2024-10-22: 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 affiliationDepartment of Pathology and Cancer Center, Stony Brook University, Stony Brook, NY 11794
contact emailomician@gmail.com
lab head
Wei Yang
contact affiliationStony Brook University
contact emailomician@gmail.com
dataset submitter
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Dataset FTP location
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