PXD044002

PXD044002 is an original dataset announced via ProteomeXchange.

Title	Darapladib, an inhibitor of Lp-PLA2, sensitises cancer cells to ferroptosis by remodelling lipid metabolism
Description	Arachidonic and adrenic acids in the membrane play key roles in ferroptosis, but how these fatty acids are manipulated in cells is largely unknown. Here, we reveal that lipoprotein-associated phospholipase A2 (Lp-PLA2) controls intracellular phospholipid metabolism and contributes to ferroptosis resistance. A metabolic drug screen revealed that darapladib, an inhibitor of Lp-PLA2, synergistically induced ferroptosis in the presence of GPX4 inhibitors. Notably, darapladib was able to enhance ferroptosis under lipoprotein-deficient or serum-free conditions. Furthermore, Lp-PLA2 was located in the membrane and cytoplasm and suppressed ferroptosis, suggesting the critical role of intracellular Lp-PLA2. Lipidomic analysis showed that darapladib treatment or deletion of PLA2G7, which encodes Lp-PLA2, generally enriched phosphatidylethanolamine (PE) species and reduced lysophosphatidylethanolamine (lysoPE) species. Moreover, combination treatment with darapladib and PACMA31, a GPX4 inhibitor, efficiently inhibited tumour growth in a xenograft model. Our study suggests that inhibition of Lp-PLA2 is a potential therapeutic strategy to enhance ferroptosis in cancer treatment.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:06:17.964.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Seoyoung Jang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-22 05:10:37	ID requested
1	2023-10-24 07:15:22	announced
⏵ 2	2023-11-14 09:06:18	announced	2023-11-14: Updated project metadata.

Oh M, Jang SY, Lee JY, Kim JW, Jung Y, Kim J, Seo J, Han TS, Jang E, Son HY, Kim D, Kim MW, Park JS, Song KH, Oh KJ, Kim WK, Bae KH, Huh YM, Kim SH, Kim D, Han BS, Lee SC, Hwang GS, Lee EW, The lipoprotein-associated phospholipase A2 inhibitor Darapladib sensitises cancer cells to ferroptosis by remodelling lipid metabolism. Nat Commun, 14(1):5728(2023) [pubmed]

submitter keyword: Lipidomics,Cancer cell, Lp-PLA2, LC-MS/MS

Geum-Sook Hwang
contact affiliation	Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Republic of Korea
contact email	gshwang@kbsi.re.kr
lab head
Seoyoung Jang
contact affiliation	Korea Basic Science Institute
contact email	jm0326@kbsi.re.kr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/10/PXD044002

PRIDE project URI

• PRIDE
  1. PXD044002
     1. Label: PRIDE project
     2. Name: Darapladib, an inhibitor of Lp-PLA2, sensitises cancer cells to ferroptosis by remodelling lipid metabolism