PXD057414-1

PXD057414 is an original dataset announced via ProteomeXchange.

Title	IDH1 Reprograms Nucleotide Metabolism by Inducing Chromatin Remodeling and DHODH Transcription to Drive Chemoresistance in Nasopharyngeal Carcinoma
Description	Metabolic reprogramming under therapeutic stress may represent a targetable vulnerability for cancer treatment. Elucidation of the metabolic alterations linked to chemotherapy in nasopharyngeal carcinoma (NPC) could uncover potential therapeutic strategies. Using proteomics and transcriptomic profiles, we identified wild-type IDH1 as a crucial metabolic enzyme upregulated in gemcitabine plus cisplatin chemotherapy (GP)-resistant NPC. IDH1 reprogrammed nucleotide metabolism in response to chemotherapy, linking DNA damage repair (DDR) to ferroptosis resistance via DHODH, thereby contributing to chemoresistance in NPC. Mechanistically, α-ketoglutarate (α-KG), a metabolite of IDH1, enhanced chromatin accessibility to promote DHODH transcription via α-KG-dependent dioxygenase ALKBH5-recruited HNRNPC. The DHODH inhibitor BAY2402234 markedly sensitized NPC cells to chemotherapy. Clinically, a prognostic model based on DDR and ferroptosis signatures effectively predicted disease relapse risk post-chemotherapy in NPC. This study links DDR to ferroptosis defense via the IDH1/α-KG/ALKBH5/DHODH axis, suggesting DHODH inhibition as a promising therapeutic strategy to overcome chemoresistance in tumors harboring wild-type IDH1.
HostingRepository	iProX
AnnounceDate	2026-01-07
AnnouncementXML	Submission_2026-08-31_20:09:28.360.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yuheng Zhao
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-31 19:28:18	ID requested
⏵ 1	2026-08-31 20:09:28	announced

Dataset with its publication pending

submitter keyword: DNA damage repair, ferroptosis, de novo pyrimidine synthesis, chemotherapy resistance, IDH1

Jun Ma
contact affiliation	Sun Yat-sen University Cancer Center
contact email	majun2@mail.sysu.edu.cn
lab head
Yuheng Zhao
contact affiliation	Sun Yat-sen University Cancer Center
contact email	zhaoyh1@sysucc.org.cn
dataset submitter

iProX dataset URI