PXD032041
PXD032041 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Drug-induced epigenomic plasticity reprograms circadian rhythm regulation to drive prostate cancer towards androgen-independence |
Description | In 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. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_07:55:34.740.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Liesbeth Hoekman |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2022-03-03 11:56:41 | ID requested | |
1 | 2022-10-14 14:59:01 | announced | |
⏵ 2 | 2023-11-14 07:55:37 | announced | 2023-11-14: 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 affiliation | Proteomics 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 email | m.altelaar@nki.nl |
lab head | |
Liesbeth Hoekman | |
contact affiliation | The Netherlands Cancer Institute, Amsterdam, The Netherlands. |
contact email | l.hoekman@nki.nl |
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/2022/10/PXD032041 |
PRIDE project URI |
Repository Record List
[ + ]