PXD047396-1

PXD047396 is an original dataset announced via ProteomeXchange.

Title	Reprogramming neuroblastoma by diet-enhanced polyamine depletion
Description	Cancer growth is fueled by nutrients obtained from circulation and local biosynthesis. Isolating and exploiting tumoral nutrient dependencies to potentiate current anti-cancer therapies is undergoing active research. We used unbiased metabolomics on patient samples and identified reprogramming of the arginine-proline-glutamine axis in MYCN amplified neuroblastoma. Tumoral acquisition of these non-essential amnio acids, as revealed by stable isotope tracing, was primarily by import, while extra-tumoral deamination of arginine indirectly feeds tumor ornithine via circulation. Dietary depletion of proline and arginine reduced systemic ornithine, the direct precursor of polyamine biosynthesis, and in combination with the clinically approved polyamine biosynthesis inhibitor, difluoromethylornithine, enhanced their depletion to improve survival in a MYCN-driven neuroblastoma mouse model. Mechanistically, ribosome profiling indicated specific translation defects, with ribosomal pausing at adenine-ending codons, to cause reprogramed protein biosynthesis affecting cell cycle and inducing neuronal differentiation. This work provides proof of concept for combined small molecule and nutrient depletion therapy for simultaneous targeting of translation in cancers dependent on external nutrient uptake.
HostingRepository	PRIDE
AnnounceDate	2025-07-24
AnnouncementXML	Submission_2025-07-24_05:26:48.280.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sarah Cherkaoui
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-30 03:10:42	ID requested
⏵ 1	2025-07-24 05:26:48	announced

Dataset with its publication pending

submitter keyword: Neuroblastoma, TH-MYCN, difluoromethylornithine

Raphael J. Morscher
contact affiliation	Pediatric Cancer Metabolism Laboratory, Children's Research Center, University of Zurich, 8032 Zurich, Switzerland. Division of Oncology, University Children's Hospital Zurich and Children's Research Center, University of Zurich, 8032 Zurich, Switzerland.
contact email	raphael.morscher@kispi.uzh.ch
lab head
Sarah Cherkaoui
contact affiliation	University Children Hospital Zurich
contact email	sarah.cherkaoui@kispi.uzh.ch
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/2025/07/PXD047396

PRIDE project URI

• PRIDE
  1. PXD047396
     1. Label: PRIDE project
     2. Name: Reprogramming neuroblastoma by diet-enhanced polyamine depletion