PXD057566

PXD057566 is an original dataset announced via ProteomeXchange.

Title	EZH2 inhibition in mesothelioma cells increases the release of extracellular vesicles that skew neutrophils toward a pro-tumor phenotype.
Description	BAP1-deficient pleural mesotheliomas have been shown to be sensitive to inhibition of the histone methyltransferase EZH2 in preclinical settings but only showed modest efficacy in clinical trials. We recently demonstrated that in BAP1-proficient mesothelioma cells, CDKN2A plays a crucial role in response to the selective EZH2 inhibitor tazemetostat. Therefore, in the current study, we employed a quantitative proteomic mass spectrometry approach to analyze changes in protein expression in response to tazemetostat in BAP1-CDKN2A proficient MSTO-211H cells cultured as spheroids. Our results demonstrate that tazemetostat treatment induced an increase in the expression of 21 proteins and a decrease in the expression of 12 proteins. Notably, RAB27b and CD63 were among the most up-regulated proteins. We also demonstrate that higher levels of RAB27b and CD63 were linked to a heightened release of extracellular vesicles (EVs). When exploring the impact of tumor-derived EVs on naïve neutrophil behavior, we found that brief exposure to EVs derived from tazemetostat-treated cells skewed naïve neutrophils toward a pro-tumor phenotype characterized by high levels of PD-L1 and mesothelin surface expression. These EV-elicited neutrophils suppressed lymphocyte proliferation while enhancing tumor cell growth. Interestingly, most up-regulated proteins in EV cargo derived from tazemetostat-treated spheroids were FZD6, the catalytic subunit alpha of PI3K and PPAR-α, while the most downregulated was ENOX2.
HostingRepository	PRIDE
AnnounceDate	2025-11-24
AnnouncementXML	Submission_2025-11-23_16:34:10.337.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marcello Manfredi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480; TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-06 00:37:31	ID requested
⏵ 1	2025-11-23 16:34:11	announced

Pinton G, Bari E, Fallarini S, Gigliotti V, De Giorgis V, Chiazza F, Torre ML, Manfredi M, Moro L, EZH2 Inhibition in Mesothelioma Cells Increases the Release of Extracellular Vesicles That Skew Neutrophils Toward a Protumor Phenotype. Int J Mol Sci, 26(21):(2025) [pubmed]

10.3390/ijms262110328;

submitter keyword: mass spectrometry,Pleural Mesothelioma, spheroids., Histone methyltransferase EZH2, CDKN2A, Extracellular vesicles

Marcello Manfredi
contact affiliation	Biological Mass Spectrometry Lab Department of Translational Medicine (DiMeT) Center for Translational Research on Autoimmune & Allergic Diseases - CAAD University of Piemonte Orientale Corso Trieste 15/A, 28100, Novara, Italy
contact email	marcello.manfredi@uniupo.it
lab head
Marcello Manfredi
contact affiliation	University of Eastern Piedmont
contact email	marcello.manfredi@uniupo.it
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/2025/11/PXD057566

PRIDE project URI

• PRIDE
  1. PXD057566
     1. Label: PRIDE project
     2. Name: EZH2 inhibition in mesothelioma cells increases the release of extracellular vesicles that skew neutrophils toward a pro-tumor phenotype.