PXD045833

PXD045833 is an original dataset announced via ProteomeXchange.

Title	CDS2 is a synthetic lethal target in mesenchymal-like cancers
Description	Synthetic lethal interactions (SLIs) based on genomic alterations in cancer have been therapeutically explored. We investigated the SLI space as a function of differential RNA expression in cancer and normal tissue. Computational analyses of functional genomic and gene expression resources uncovered a cancer-specific SLI between the paralogs cytidine diphosphate diacylglycerol synthase 1 (CDS1) and CDS2. The essentiality of CDS2 for cell survival is observed for mesenchymal-like cancers, which express low levels of CDS1 and account for roughly half of all cancers. We confirm the CDS1-2 SLI in cultured cancer cell lines and tumor-bearing mice. Mechanistically, the CDS1-2 SLI is accompanied by disruption of lipid homeostasis, including accumulation of cholesterol esters and triglycerides, and apoptosis. Genome-wide CRISPR-Cas9 knockout screens in CDS1-negative cancer cells identify no common escape mechanism of death caused by CDS2 ablation, indicating the robustness of the SLI. Synthetic lethality is driven by CDS2 dosage and depends on catalytic activity. Thus, CDS2 may serve as a pharmacologically tractable target in mesenchymal-like cancers.
HostingRepository	PRIDE
AnnounceDate	2025-04-22
AnnouncementXML	Submission_2025-04-22_06:02:14.336.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Onno Bleijerveld
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-29 16:04:12	ID requested
1	2025-03-31 23:59:16	announced
2	2025-04-11 06:42:52	announced	2025-04-11: Updated project metadata.
⏵ 3	2025-04-22 06:02:14	announced	2025-04-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: synthetic lethal interactions, CDS2, DIA, mesenchymal cancers, proteome, LC-MS/MS

Onno Bleijerveld
contact affiliation	NKI Proteomics Facility, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands
contact email	o.bleijerveld@nki.nl
lab head
Onno Bleijerveld
contact affiliation	The Netherlands Cancer Institute
contact email	o.bleijerveld@nki.nl
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/2025/03/PXD045833

PRIDE project URI

• PRIDE
  1. PXD045833
     1. Label: PRIDE project
     2. Name: CDS2 is a synthetic lethal target in mesenchymal-like cancers