PXD055446

PXD055446 is an original dataset announced via ProteomeXchange.

Title	VIPAS39 confers ferroptosis resistance in ovarian cancer through exporting ACSL4
Description	Ovarian cancer (OC), particularly its epithelial subtype (EOC), is the most lethal gynecological malignancy worldwide, with the majority of patients diagnosed at an advanced stage and a five-year survival rate below 30%. The standard treatment, primarily consisting of cytoreductive surgery and platinum-based chemotherapy, often leads to recurrence and metastasis, highlighting the urgent need for innovative therapeutic approaches. Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, offers a promising avenue due to cancer cells’ heightened susceptibility compared to non-cancerous cells. This susceptibility is due to their increased iron requirements and the resultant vulnerability to peroxidation of polyunsaturated fatty acids in cell membranes. Notably, acyl-CoA synthase long-chain family member 4 (ACSL4) plays a pivotal role in this process by catalyzing the esterification of free fatty acids into membrane phospholipids, a critical step for ferroptosis induction. Our study explores the synergistic effects of interferon-gamma (IFN-γ) and arachidonic acid (AA), natural inducers of ferroptosis that increase ACSL4 expression and activity, thereby promoting cell death in EOC. We demonstrate that while some EOC cell lines are highly responsive to IFN-γ and AA, indicating effective ferroptosis induction, others show resistance, likely due to the secretion of ACSL4 via exosomes. This resistance is mediated by VIPAS39, a protein crucial for protein sorting in the endosomal pathway and exosome biogenesis. Inhibiting VIPAS39 may thus enhance the sensitivity of resistant ovarian cancer cells to ferroptosis-inducing treatments, presenting a novel therapeutic strategy to curb ovarian cancer progression. This study provides foundational insights into the heterogeneous response of EOC cells to ferroptosis and underscores the potential of targeting vesicular trafficking processes to overcome drug resistance.
HostingRepository	iProX
AnnounceDate	2024-08-30
AnnouncementXML	Submission_2025-12-28_16:56:02.797.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yuening Jiang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-01 20:29:45	ID requested
⏵ 1	2025-12-28 16:56:03	announced

Jiang Y, Li J, Wang T, Gu X, Li X, Liu Z, Yue W, Li M, VIPAS39 confers ferroptosis resistance in epithelial ovarian cancer through exporting ACSL4. EBioMedicine, 114():105646(2025) [pubmed]

submitter keyword: ovarian cancer, ferroptosis, exosome, ACSL4, VIPAS39

Mo Li
contact affiliation	Peking University Third Hospital
contact email	limo@hsc.pku.edu.cn
lab head
Yuening Jiang
contact affiliation	Peking University Third Hospital
contact email	2111110435@stu.pku.edu.cn
dataset submitter

iProX dataset URI