PXD053752

PXD053752 is an original dataset announced via ProteomeXchange.

Title	Targeting the CDS1/2 axis as a therapeutic strategy in uveal melanoma and pan-cancer
Description	Metastatic uveal melanoma is an aggressive disease with limited effective therapeutic options. To comprehensively map monogenic and digenic dependencies, we performed CRISPR-Cas9 screening in ten extensively profiled human uveal melanoma cell line models using genome-wide single gene/gRNA and combinatorial paired gene/paired gRNA CRISPR libraries. Within our identified uveal melanoma-specific essential genes and synthetic lethal gene pairs, we identified and validated CDS2 as a novel genetic dependency in the context of low CDS1 expression. We further demonstrate that CDS1/CDS2 is a synthetic lethal interaction in vivo and reveal that CDS2 knockout results in the disruption of phosphoinositide synthesis, cellular apoptosis, and that re-expression of CDS1 rescues the cell fitness defect provoked by CDS2 loss. We extend our analysis using pan-cancer data confirming increased CDS2 essentiality in diverse tumour types with low CDS1 expression. Our results suggest that CDS2 inhibition should be investigated as a therapeutic strategy in uveal melanoma that may extend to multiple tumour types with low CDS1 expression. The data provided in this dataset explore the effect of CDS2 loss in uveal melanoma cell lines.
HostingRepository	PRIDE
AnnounceDate	2025-04-01
AnnouncementXML	Submission_2025-04-01_04:13:47.902.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Graeme Benstead-Hume
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Ascend

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-08 05:24:05	ID requested
⏵ 1	2025-04-01 04:13:48	announced

Dataset with its publication pending

submitter keyword: CDS1, , CDS2, uveal melanom

Jyoti Choudhary
contact affiliation	Functional Proteomics, ICR
contact email	jyoti.choudhary@icr.ac.uk
lab head
Graeme Benstead-Hume
contact affiliation	ICR
contact email	ghume@icr.ac.uk
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/2025/04/PXD053752

PRIDE project URI

• PRIDE
  1. PXD053752
     1. Label: PRIDE project
     2. Name: Targeting the CDS1/2 axis as a therapeutic strategy in uveal melanoma and pan-cancer