PXD031768

PXD031768 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-21 02:41:05	ID requested
⏵ 1	2025-04-12 01:53:27	announced

Dataset with its publication pending

submitter keyword: KDM4C, Triple negative breast cancer, histone tail clipping, cathepsin L, GRHL2

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

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/2025/04/PXD031768

PRIDE project URI

• PRIDE
  1. PXD031768
     1. Label: PRIDE project
     2. Name: KDM4C histone demethylase connects chromatin remodeling and metabolism in triple-negative breast cancer