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PXD031768

PXD031768 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleKDM4C histone demethylase connects chromatin remodeling and metabolism in triple-negative breast cancer
DescriptionTriple-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.
HostingRepositoryPRIDE
AnnounceDate2025-04-12
AnnouncementXMLSubmission_2025-04-12_01:53:27.126.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEvangelia Papachristou
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; deamidated residue
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-02-21 02:41:05ID requested
12025-04-12 01:53:27announced
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 affiliationHarvard Medical School Department of Medical Oncology Dana-Farber Cancer Institute 450 Brookline Ave. SM1070 Boston, MA 02215
contact emailKornelia_Polyak@dfci.harvard.edu
lab head
Evangelia Papachristou
contact affiliationSenior Scientific Assistant
contact emailEva.Papachristou@cruk.cam.ac.uk
dataset submitter
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Dataset FTP location
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PRIDE project URI
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