PXD056104

PXD056104 is an original dataset announced via ProteomeXchange.

Title	Unique structural configuration of EV-DNA primes Kupffer cell-mediated anti-tumor immunity to prevent metastatic progression
Description	Extracellular vesicles (EVs) transport biomolecules that mediate intercellular communication. We previously showed that EVs contain DNA (EV-DNA) representing the entire genome. However, the mechanism of EV-DNA packaging and its role in cancer remains elusive. Here, we demonstrate that the majority of DNA is localized on the vesicle surface and associated with uniquely modified and cleaved histones. We conducted a genome-wide CRISPR knockout screen, which revealed that immune developmental pathways and genes, including APAF1 and NCF1, regulated EV-DNA packaging. We further demonstrated in colorectal cancer models that uptake of EVs and EV-DNA by Kupffer cells (KC) activated DNA damage responses. This activation re-wired KC cytokine production and generated tertiary lymphoid structures in pre-metastatic livers, thereby suppressing metastasis. Conversely, loss of APAF1 decreased EV-DNA packaging and promoted liver metastasis. Quantifying EV-DNA in colorectal cancer biopsies revealed that EV-DNA could possibly serve as a predictive biomarker for metastatic risk.
HostingRepository	PRIDE
AnnounceDate	2024-09-23
AnnouncementXML	Submission_2024-09-23_14:18:31.961.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Simone Sidoli
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue; acetylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-23 14:13:48	ID requested
⏵ 1	2024-09-23 14:18:32	announced

Dataset with its publication pending

submitter keyword: histone, PTMs,EV-DNA, Kupffer

Simone Sidoli
contact affiliation	Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, United States
contact email	simone.sidoli@einsteinmed.edu
lab head
Simone Sidoli
contact affiliation	Albert Einstein College of Medicine
contact email	simone.sidoli@gmail.com
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/2024/09/PXD056104

PRIDE project URI

• PRIDE
  1. PXD056104
     1. Label: PRIDE project
     2. Name: Unique structural configuration of EV-DNA primes Kupffer cell-mediated anti-tumor immunity to prevent metastatic progression