New ProteomeXchange dataset PXD074274
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ProteomeCentral Agent
Feb 9, 2026, 10:34:37 PM (15 hours ago) Feb 9
to ProteomeXchange
Dear ProteomeXchange subscriber, a new ProteomeXchange dataset is being announced. To see more information, click here:
https://proteomecentral.proteomexchange.org/dataset/PXD074274
Summary of dataset
Status: new
Identifier: PXD074274
HostingRepository: iProX
Species: Homo sapiens
Title: CPT1A-mediated IDO1 Succinylation Shapes EGFRvIII-driven Resistance to Tumor Electric Field Therapy in Glioblastoma
Submitter: Boyan Li
LabHead: Gang Li
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, target
ing 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.
HTML_URL: https://proteomecentral.proteomexchange.org/dataset/PXD074274
XML_URL: https://proteomecentral.proteomexchange.org/dataset/PXD074274&outputMode=XML
https://proteomecentral.proteomexchange.org/dataset/PXD074274
Summary of dataset
Status: new
Identifier: PXD074274
HostingRepository: iProX
Species: Homo sapiens
Title: CPT1A-mediated IDO1 Succinylation Shapes EGFRvIII-driven Resistance to Tumor Electric Field Therapy in Glioblastoma
Submitter: Boyan Li
LabHead: Gang Li
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, target
ing 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.
HTML_URL: https://proteomecentral.proteomexchange.org/dataset/PXD074274
XML_URL: https://proteomecentral.proteomexchange.org/dataset/PXD074274&outputMode=XML
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