PXD046736

PXD046736 is an original dataset announced via ProteomeXchange.

Title	TRIM24 as therapeutic target in endocrine treatment resistant breast cancer
Description	While ERα+ breast cancer treatment is considered effective, resistance to endocrine therapy is common. Since in therapy-resistance tumors, ERα is still the main driver, alternative therapeutic strategies are needed to disrupt ERα transcriptional activity. In this work, we describe TRIM24 as a key player of the ERα transcriptional complex. TRIM24 interacts with ERα and other well-known ERα-cofactors to facilitate ERα chromatin interactions, and allows for maintenance of active histone marks including H3K23ac and H3K27ac. Consequently, genetic perturbation of TRIM24 abrogates ERα-driven transcriptional programs and reduces tumor cell proliferation capacity. Using a recently-developed PROTAC targeting TRIM24, ERα-driven transcriptional output and growth was blocked, effectively treating not only endocrine-responsive cell lines, but also drug resistant derivates thereof as well as cell line models bearing activating ESR1 point mutations. Finally, using human tumor-derived organoid models, we could show efficacy of TRIM24 PROTAC in the endocrine responsive and resistant setting, with no response in ERα-negative organoids. Overall, our study positions TRIM24 as a central component for integrity and activity of the ERα transcriptional complex, with PROTAC-mediated perturbation of TRIM24 as promising therapeutic avenue in the treatment of primary and endocrine resistance breast cancer.
HostingRepository	PRIDE
AnnounceDate	2025-08-01
AnnouncementXML	Submission_2025-08-01_06:18:58.200.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 Exploris 480; Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-07 04:48:30	ID requested
⏵ 1	2025-08-01 06:18:58	announced

Dataset with its publication pending

submitter keyword: ERα, PROTAC, therapy resistant breast cancer

Onno Bleijerveld
contact affiliation	Mass Spectrometry/Proteomics Facility, Netherlands Cancer Institute, Amsterdam, Netherlands.
contact email	o.bleijerveld@nki.nl
lab head
Liesbeth Hoekman
contact affiliation	The Netherlands Cancer Institute, Amsterdam, The Netherlands.
contact email	l.hoekman@nki.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD046736
     1. Label: PRIDE project
     2. Name: TRIM24 as therapeutic target in endocrine treatment resistant breast cancer