PXD074274

PXD074274 is an original dataset announced via ProteomeXchange.

Title	CPT1A-mediated IDO1 Succinylation Shapes EGFRvIII-driven Resistance to Tumor Electric Field Therapy in Glioblastoma
Description	Tumor Electric Field Therapy (TEFT) represents a biophysical modality that disrupts mitosis in glioblastoma (GBM). However, clinical responses show heterogeneous. Here, we report that EGFRvIII as a critical determinant of TEFT resistance through a retrospective analysis of a maintained clinical cohort. Mechanistically, TEFT-induced bioenergetic stress triggers an AMPK-PPARα signaling axis that leads to the compensatory upregulation of the mitochondrial enzyme CPT1A. We found that CPT1A exerts a non-canonical lysine succinyltransferase (LSTase) activity to catalyze the specific succinylation of IDO1 at Lysine 377. This modification prevents TRIM21-mediated ubiquitination and proteasomal degradation of IDO1. Stabilized IDO1 subsequently activates aryl hydrocarbon receptor (AhR) signaling, which transcriptionally upregulates the mitotic regulators DCLK1 and ARHGEF2 to fortify spindle and microtubule architecture against biophysical disruption. In preclinical models, targeting this metabolic-structural axis with the third-generation EGFR inhibitor osimertinib abrogated resistance and restored sensitivity to TEFT. Furthermore, a proof-of-concept case series demonstrated that combinatorial therapy with osimertinib and TEFT elicited significant radiological regression in patients with recurrent EGFRvIII-driven GBM. Our findings uncover a convergent resistance mechanism linking metabolic plasticity to cytoskeletal remodeling, establish a mechanism-based therapeutic strategy for this refractory subtype.
HostingRepository	iProX
AnnounceDate	2026-02-09
AnnouncementXML	Submission_2026-02-09_19:34:34.538.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Boyan Li
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ; Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-09 19:33:55	ID requested
⏵ 1	2026-02-09 19:34:35	announced

Dataset with its publication pending

submitter keyword: glioblastoma, Tumor Electric Field Therapy, Succinylation

Gang Li
contact affiliation	Qilu Hospital of Shandong University
contact email	dr.ligang@sdu.edu.cn
lab head
Boyan Li
contact affiliation	Qilu Hospital of Shandong University
contact email	liboyan@email.sdu.edu.cn
dataset submitter

iProX dataset URI