PXD062252-1

PXD062252 is an original dataset announced via ProteomeXchange.

Title	FBXW7 Mutations Reprograms Glucose Metabolism by Activating the ETV6-GLUT Axis in Endometrial Cancer
Description	Endometrial cancer (EC) progression involves metabolic reprogramming, frequently driven by mutations in key tumor suppressors and oncogenes. In this study, we identify a previously unrecognized pathway through which FBXW7 mutations rewire glucose metabolism in EC cells. Specifically, we demonstrate that loss-of-function mutations in FBXW7 disrupt the SCFFBXW7 E3 ubiquitin ligase complex, leading to the stabilization of the transcription factor ETV6 by inhibiting its ubiquitin-mediated degradation. Accumulated ETV6 subsequently enhances the transcriptional activation of glucose transporter 1 (GLUT1), elevating its expression and localization to the plasma membrane. This increased GLUT1 expression significantly enhances glucose uptake, fueling both aerobic glycolysis and oxidative phosphorylation, which collectively accelerate EC cell proliferation and tumor growth. Importantly, targeting GLUT1 pharmacologically reverses the proliferative advantage conferred by ETV6 overexpression, highlighting a promising therapeutic vulnerability. Our findings establish the FBXW7-ETV6-GLUT1 regulatory axis as a critical driver of metabolic adaptation and tumor progression, offering potential strategies for targeted therapy in FBXW7-mutant EC.
HostingRepository	iProX
AnnounceDate	2025-03-25
AnnouncementXML	Submission_2025-06-29_21:09:13.127.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Siqi Fei
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-26 01:18:27	ID requested
⏵ 1	2025-06-29 21:09:13	announced

Dataset with its publication pending

submitter keyword: FBXW7, Ubiquitination, Glucose metabolism, Endometrial caner

Chenji Wang
contact affiliation	School of Life Sciences, Fudan University
contact email	chenjiwang@fudan.edu.cn
lab head
Siqi Fei
contact affiliation	School of Life Sciences, Fudan University
contact email	feisiqifufu@163.com
dataset submitter

iProX dataset URI