PXD068676

PXD068676 is an original dataset announced via ProteomeXchange.

Title	Exosomal Proteomics Reveals Fatty Acid Metabolism Linked to Gefitinib Resistance in Non-Small Cell Lung Cancer
Description	Extracellular vesicles (EVs) serve as critical mediators of intercellular communication, facilitating drug resistance in tumor microenvironments by transferring bioactive components like proteins. Despite their potential role in non-small cell lung cancer (NSCLC), systematic investigations into exosome-mediated mechanisms underlying gefitinib resistance remain limited. In this study, we demonstrated that EVs contribute to enhanced drug tolerance, prompting a comprehensive proteomic analysis of both parental HCC827 cells and their exosomal counterparts. Proteomic profiling identified 4,098 exosome proteins, with 3,765 overlapping with cellular proteins. Fatty acid metabolism pathways were significantly enriched among proteins upregulated in resistant cells and EVs, with some enzymes showing pronounced correlations with resistance, particularly ACC1, whose expression levels were nearly eight times higher in resistant cells. Functional interventions demonstrated that either pharmacological inhibition of ACC1 with Firsocostat or siRNA-mediated ACC1 knockdown significantly reduced the gefitinib IC50 in HCC827/GR cells. This effect was associated with reduced ACC1 expression, alongside a partial restoration of fatty acid oxidation (FAO) activity in HCC827/GR cells and the reestablishment of their sensitivity to gefitinib-induced elevation of reactive oxygen species (ROS), ultimately reversing the drug-resistant phenotype.
HostingRepository	PRIDE
AnnounceDate	2025-12-29
AnnouncementXML	Submission_2025-12-28_16:44:40.547.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhang yuanyuan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-22 03:33:59	ID requested
⏵ 1	2025-12-28 16:44:41	announced

Zhang Y, Zhu W, Zhu J, Hu R, Yang Y, Exosomal proteomics reveals fatty acid metabolism linked to gefitinib resistance in non-small cell lung cancer. Cell Biol Toxicol, 42(1):3(2025) [pubmed]

10.1007/s10565-025-10121-8;

submitter keyword: NSCLC, Proteomics, Exosomes, Gefitinib resistance, Fatty acid metabolism

Yang Yunhuang
contact affiliation	University of Chinese Academy of Sciences
contact email	yang_yh@apm.ac.cn
lab head
Zhang yuanyuan
contact affiliation	Huazhong University of Science and Technology
contact email	2450739303@qq.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD068676
     1. Label: PRIDE project
     2. Name: Exosomal Proteomics Reveals Fatty Acid Metabolism Linked to Gefitinib Resistance in Non-Small Cell Lung Cancer