⮝ Full datasets listing

PXD056852

PXD056852 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleNNMT mediates sensitivity to NAD(H) lowering agents in prostate cancer cells with mesenchymal phenotype
DescriptionCastration-resistant prostate cancer (CRPC) refers to a population of prostate cancer patients who are no longer responsive to androgen deprivation therapy (ADT). Metastatic CRPC is currently lethal, underscoring the urgent need to identify novel therapeutical targets to reverse disease outcome. Unresponsiveness to ADT is multifactorial and often associated with prostate cancer cell’s plasticity, leading to the arise of several CRPC subtypes, which should be individually address for the identification of targetable vulnerabilities. Particularly, the development of mesenchymal stem-like phenotypes is associated with CRPC. The Yes-associated protein (YAP) is an effector of the Hippo tumor suppressor pathway, whose deregulation is associated with CRPC. Here we showed that YAP depletion in mesenchymal stem-cell like PC cells leads to the downregulation of proteins previously associated with epithelial to mesenchymal transdifferentiation (EMT), including N-methylnicotinamide transferase (NNMT). NNMT is also involved in cellular energetics, by competing with nicotinamide phosphoribosyltransferase (NAMPT) for nicotinamide. Thus, we found that mesenchymal-like prostate cancer cells with upregulation of NAMPT, but not epithelial ones, are sensitive to NAMPT inhibition (FK866). NNMT depletion counteracts FK866 toxicity by maintaining cellular nicotinamide levels. Moreover, we identified NNMT as a marker of a subtype of CRPC with stem-cell properties (CRPC-SCL) in which YAP is a main targetable vulnerability. Transcriptomics analysis of a murine-derived prostate cancer cell line exposed to stem cell conditions (DVL3-SCM), unraveled a strong upregulation of NNMT transcripts, in comparison to the parental counterpart (DVL3-PAR). DVL3-SCM presented an increased mesenchymal phenotype and aggressiveness in vitro. In conclusion, we found a specific vulnerability of a subpopulation of CRPC showing that NAMPT inhibition can be an effective molecular targeting strategy to overcome therapy resistant metastatic PC cells with mesenchymal, YAP dependent, phenotype. Notably, the efficacy of NAMPT targeting is potentiated by its dependency on YAP NNMT expression.
HostingRepositoryPRIDE
AnnounceDate2025-02-24
AnnouncementXMLSubmission_2025-02-24_01:32:27.257.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD056852
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterRomina Belli
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-10-16 04:50:34ID requested
12025-02-24 01:32:27announced
Publication List
10.6019/PXD056852;
Keyword List
submitter keyword: NNMT, EMT, CRPC-SCL,NAMPT, YAP, FK866, Stemness
Contact List
Alessandro Provenzani
contact affiliationUniversity of Trento, Department CIBIO - Laboratory of Genomic Screening, Trento, Italy
contact emailalessandro.provenzani@unitn.it
lab head
Romina Belli
contact affiliationUniversity of Trento
contact emailromina.belli@unitn.it
dataset submitter
Full Dataset Link List
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/2025/02/PXD056852
PRIDE project URI
Repository Record List
[ + ]