PXD056104 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-09-23 14:13:48 | ID requested | |
⏵ 1 | 2024-09-23 14:18:32 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: histone, PTMs,EV-DNA, Kupffer |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD056104
- Label: PRIDE project
- Name: Unique structural configuration of EV-DNA primes Kupffer cell-mediated anti-tumor immunity to prevent metastatic progression