PXD031768 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | KDM4C histone demethylase connects chromatin remodeling and metabolism in triple-negative breast cancer |
Description | Triple-negative breast cancer (TNBC) is a highly aggressive disease with inferior prognosis necessitating the discovery of novel actionable targets. Here, we show that KDM4C, a histone demethylase amplified in a subset of TNBC, is a driver of TNBC tumor growth. Integrative multi-omic analysis demonstrated that KDM4C inhibition triggers chromatin and transcriptomic remodeling without substantial changes of its canonical substrates H3K9me3 and H3K36me3. Rather KDM4C loss caused proteolytic cleavage of histone H3 mediated by cathepsin L (CTSL) recruited to the chromatin by GRHL2. Metabolomic profiling showed reduced glutathione levels following KDM4C inhibition partly due to a decrease in glutamate-cysteine ligase (GCLC) leading to increased reactive oxygen species and activation of CTSL. The expression of KDM4C and GCLC correlated in TNBC and combined targeting of KDM4C and GSH axis improved response to cisplatin in TNBC. Our study reveals a novel, non-canonical role for KDM4C in TNBC that links metabolic and epigenetic profiles. |
HostingRepository | PRIDE |
AnnounceDate | 2025-04-12 |
AnnouncementXML | Submission_2025-04-12_01:53:27.126.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Evangelia Papachristou |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; deamidated residue |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-02-21 02:41:05 | ID requested | |
⏵ 1 | 2025-04-12 01:53:27 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: KDM4C, Triple negative breast cancer, histone tail clipping, cathepsin L, GRHL2 |
Contact List
Kornelia Polyak |
contact affiliation | Harvard Medical School Department of Medical Oncology Dana-Farber Cancer Institute 450 Brookline Ave. SM1070 Boston, MA 02215 |
contact email | Kornelia_Polyak@dfci.harvard.edu |
lab head | |
Evangelia Papachristou |
contact affiliation | Senior Scientific Assistant |
contact email | Eva.Papachristou@cruk.cam.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD031768
- Label: PRIDE project
- Name: KDM4C histone demethylase connects chromatin remodeling and metabolism in triple-negative breast cancer