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PXD042498-2

PXD042498 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTotal Proteome: Ergolide Mediates Anti-Cancer Effects on Metastatic Uveal Melanoma Cells and Modulates their Cell Lysate and Extracellular Vesicle proteomes.
DescriptionUveal melanoma is a poor prognosis cancer with an imperative need for new treatment options. Ergolide, a sesquiterpene lactone isolated from the flowers of Inula species (a medicinal herb), exerts anti-cancer properties. The objective of this study was to 1) evaluate whether ergolide reduced metastatic uveal melanoma (MUM) cell survival/viability in vitro and in vivo; and 2) to understand the molecular mechanism of ergolide action. Ergolide treatment resulted in significant dose-dependent reduction (48.5 to 99.9%; p < 0.0001) in OMM2.5 cell survival in vitro and of normalized primary zebrafish xenograft fluorescence (56%; p< 0.0001) in vivo, compared to vehicle controls. Proteome profiling of ergolide treated OMM2.5 cells, identified 5023 proteins in total with 52 and 55 proteins significantly altered at 4 hours and 24 hours, respectively (p value <0.05; fold-change >1.2). Immunoblot analysis of heme oxygenase 1 (HMOX1), growth/differentiation factor 15 (GDF15) and macrophage migration inhibitory factor (MIF) corroborated the proteomics data. MIF was distinctly downregulated following ergolide treatment. Proteomics of EVs isolated from OMM2.5 cells treated with ergolide detected 2931 total proteins, 2679 of which are recognized as EV proteins based on the Vesiclepedia compendium. 252 additional putative novel EV proteins were also identified. Within the differentially expressed proteins, the proteasomal pathway was primarily altered. Interestingly, BRCA2 and CDKN1A Interacting Protein (BCCIP) and Chitinase Domain Containing 1 (CHID1), were the only proteins significantly differentially expressed by ergolide in both the OMM2.5 cell and EV isolates and they displayed inverse differential expression in the cells versus the EVs. In the TCGA database, no significant correlations occurred between BCCIP and CHID1 transcript levels and overall survival or disease-free survival in UM patients. Ergolide is a novel candidate that shows promise as an anti-proliferative agent for UM/MUM cells. Proteomic profiling of OMM2.5 cell lysates and EVs identified candidate pathways elucidating the action of ergolide and putative biomarkers of UM, that require further examination.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:56:31.989.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKieran Wynne
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-05-25 07:37:17ID requested
12024-08-26 06:38:07announced
22024-10-22 06:56:32announced2024-10-22: Updated project metadata.
Publication List
Sundaramurthi H, Tonelotto V, Wynne K, O'Connell F, O'Reilly E, Costa-Garcia M, Kov, á, csh, á, zi C, Kittel A, Marcone S, Blanco A, Pallinger E, Hambalk, ó S, Piulats Rodriguez JM, Ferdinandy P, O'Sullivan J, Matallanas D, Jensen LD, Giricz Z, Kennedy BN, Ergolide mediates anti-cancer effects on metastatic uveal melanoma cells and modulates their cellular and extracellular vesicle proteomes. Open Res Eur, 3():88(2023) [pubmed]
10.12688/openreseurope.15973.2;
Keyword List
ProteomeXchange project tag: Cancer (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project
submitter keyword: Melanoma,Erglotide, Q Exactive, Proteomics
Contact List
Breandán N. Kennedy
contact affiliationProfessor School of Biomolecular and Biomedical Science, University College Dublin, School of Biomolecular and Biomedical Science, Conway Institute Belfield Dublin 4
contact emailbrendan.kennedy@ucd.ie
lab head
Kieran Wynne
contact affiliationUniversity College Dublin
contact emailkieran.wynne1@ucd.ie
dataset submitter
Full Dataset Link List
Dataset FTP location
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