PXD058176-1

PXD058176 is an original dataset announced via ProteomeXchange.

Title	AKT1 confers tumor resistance to cuproptosis by phosphorylating FDX1
Description	Cuproptosis, a recently defined copper-dependent cell death, remains largely unexplored in tumor therapies, particularly in breast cancer. Our study demonstrates that triple-negative breast cancer (TNBC) bears a relative elevated copper levels and exhibit resistance to cuproptosis. Mechanistically, cooper activates AKT1 signaling pathway, which inhibits cuproptosis by directly phosphorylating ferredoxin-1 (FDX1), a key regulator involved in cuproptosis. AKT1-mediated FDX1 phosphorylation abrogates FDX1-induced cuproptosis and aerobic respiration, accompanied by promoting glycolysis. Consequently, combination of AKT1 inhibitors MK2206 and the copper ionophore elesclomol (ES) synergistically inhibits TNBC tumorigenesis both in vitro and in vivo. In summary, our findings uncover a critical mechanism underlying TNBC resistance to cuproptosis and propose a potential therapeutic approach for TNBC.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_05:00:19.737.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	sun zicheng
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ FT

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-22 06:29:55	ID requested
⏵ 1	2025-05-07 05:00:20	announced

Sun Z, Xu H, Lu G, Yang C, Gao X, Zhang J, Liu X, Chen Y, Wang K, Guo J, Li J, AKT1 Phosphorylates FDX1 to Promote Cuproptosis Resistance in Triple-Negative Breast Cancer. Adv Sci (Weinh), 12(17):e2408106(2025) [pubmed]

10.1002/advs.202408106;

submitter keyword: cuproptosis

Zicheng Sun
contact affiliation	Sun Yat-sen University
contact email	sunzch3@mail2.sysu.edu.cn
lab head
sun zicheng
contact affiliation	Sun Yat-sen University
contact email	sunzch3@mail2.sysu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD058176
     1. Label: PRIDE project
     2. Name: AKT1 confers tumor resistance to cuproptosis by phosphorylating FDX1