PXD078876

PXD078876 is an original dataset announced via ProteomeXchange.

Title	Forced expression of uncoupling protein 1 (UCP1) counteracts the compromised activity of NK cells by tumor microenvironment
Description	Uncoupling protein 1 (UCP1) is a mitochondrial inner membrane protein whose main function is to mediate non-shivering thermogenesis. Dysregulated expression of UCP1 contributes to the pathogenesis of multiple diseases, including cancer. Natural killer (NK) cells, key effectors of antitumor immunity, are substantially impaired in the tumor microenvironment (TME). Here, we showed that UCP1 expression is markedly downregulated in tumor-infiltrating NK (TINK) cells from both colorectal cancer (CRC) patients and tumor-bearing mice and is correlated with impaired effector function. In the TME, TGF-β1 and hypoxia repress the transcription of UCP1 through the downregulation of C/EBPβ. NK cell-specific ablation of UCP1 accelerated tumor growth and reduced the infiltration of TINKs. RNA sequencing revealed an increase in NLRP3 inflammasome-mediated pyroptosis in Ucp1–/– NK cells. UCP1 deficiency synergized with TME stress to increase the uptake of fatty acids and oxidative phosphorylation via the upregulation of CD36/FABP4. This induces mitochondrial damage and excessive release of mitochondrial DNA (mtDNA), triggering the activation of the NLRP3 inflammasome and NK cell pyroptosis. Enforced UCP1 expression in NK cells prevents TME-induced pyroptosis, maintains the antitumor activity in both murine models and patient-derived organoids. Genetically modified expression of UCP1 in NK cells is a potential therapy for patients with tumors.
HostingRepository	iProX
AnnounceDate	2026-05-26
AnnouncementXML	Submission_2026-05-26_20:06:02.979.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Min Gu
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2026-05-26 20:04:37	ID requested
⏵ 1	2026-05-26 20:06:03	announced

Dataset with its publication pending

submitter keyword: UCP1, NK cells, Pyroptosis, Tumor, Therapy

Weijuan Gong
contact affiliation	Yangzhou University
contact email	wjgong@yzu.edu.cn
lab head
Min Gu
contact affiliation	Yangzhou University
contact email	19895320816@163.com
dataset submitter

iProX dataset URI