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PXD032041

PXD032041 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDrug-induced epigenomic plasticity reprograms circadian rhythm regulation to drive prostate cancer towards androgen-independence
DescriptionIn prostate cancer, androgen receptor (AR)-targeting agents are very effective in various stages of the disease. However, therapy resistance inevitably occurs and little is known about how tumor cells adapt to bypass AR suppression. Here, we performed integrative multi-omics analyses on tissues isolated before and after 3 months of AR-targeting enzalutamide monotherapy from high-risk prostate cancer patients enrolled in a neoadjuvant clinical trial. Transcriptomic analyses demonstrated that AR inhibition drove tumors towards a neuroendocrine-like disease state. In addition, epigenomic profiling revealed massive enzalutamide-induced reprogramming of pioneer factor FOXA1 – from inactive chromatin binding sites towards active cis-regulatory elements that dictate pro-survival signals. Notably, treatment-induced FOXA1 sites were enriched for the circadian rhythm core component ARNTL. Post-treatment ARNTL levels associated with poor outcome, and ARNTL suppression decreased cell growth in vitro. Our data highlight a remarkable cistromic plasticity of FOXA1 following AR-targeted therapy, and revealed an acquired dependency on circadian regulator ARNTL, a novel candidate therapeutic target.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_07:55:34.740.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterLiesbeth Hoekman
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-03-03 11:56:41ID requested
12022-10-14 14:59:01announced
22023-11-14 07:55:37announced2023-11-14: Updated project metadata.
Publication List
Linder S, Hoogstraat M, Stelloo S, Eickhoff N, Schuurman K, de Barros H, Alkemade M, Bekers EM, Severson TM, Sanders J, Huang CF, Morova T, Altintas UB, Hoekman L, Kim Y, Baca SC, Sj, ö, str, ö, m M, Zaalberg A, Hintzen DC, de Jong J, Kluin RJC, de Rink I, Giambartolomei C, Seo JH, Pasaniuc B, Altelaar M, Medema RH, Feng FY, Zoubeidi A, Freedman ML, Wessels LFA, Butler LM, Lack NA, van der Poel H, Bergman AM, Zwart W, Drug-Induced Epigenomic Plasticity Reprograms Circadian Rhythm Regulation to Drive Prostate Cancer toward Androgen Independence. Cancer Discov, 12(9):2074-2097(2022) [pubmed]
Keyword List
submitter keyword: FOXA1, prostate cancer, androgen receptor(AR), enzalutamide,LC-MSMS,ARNTL
Contact List
Maarten Altelaar
contact affiliationProteomics Facility, Netherlands Cancer Institute, Amsterdam, Netherlands. & Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht Institute for Pharmaceutical Sciences, Utrecht University and Netherlands Proteomics Centre, Utrecht, The Netherlands.
contact emailm.altelaar@nki.nl
lab head
Liesbeth Hoekman
contact affiliationThe Netherlands Cancer Institute, Amsterdam, The Netherlands.
contact emaill.hoekman@nki.nl
dataset submitter
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