PXD037464-1

PXD037464 is an original dataset announced via ProteomeXchange.

Title	Dynamic partitioning of branched-chain amino acids- derived nitrogen supports renal cancer progression
Description	Metabolic reprogramming is critical for tumor initiation and progression. However, the exact impact of specific metabolic changes on cancer progression is poorly understood. Here, we integrate multimodal analyses of primary and metastatic clonally-related clear cell renal cancer cells (ccRCC) grown in physiological media to identify key stage-specific metabolic vulnerabilities. We show that a VHL loss-dependent reprogramming of branched-chain amino acid catabolism sustains the de novo biosynthesis of aspartate and arginine enabling tumor cells with the flexibility of partitioning the nitrogen of the amino acids depending on their needs. Importantly, we identify the epigenetic reactivation of argininosuccinate synthase (ASS1), a urea cycle enzyme suppressed in primary ccRCC, as a crucial event for metastatic renal cancer cells to acquire the capability to generate arginine, invade in vitro and metastasize in vivo. Overall, our study uncovers a mechanism of metabolic flexibility occurring during ccRCC progression, paving the way for the development of novel stage-specific therapies.
HostingRepository	PRIDE
AnnounceDate	2022-11-09
AnnouncementXML	Submission_2022-11-09_07:26:45.805.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alexvon kriegsheim
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-15 14:38:34	ID requested
⏵ 1	2022-11-09 07:26:46	announced

Dataset with its publication pending

submitter keyword: Metabolism, Renal Cancer

Alex vonKriegsheim
contact affiliation	University of Edinburgh
contact email	avonkri@ed.ac.uk
lab head
Alexvon kriegsheim
contact affiliation	University of Edinburgh
contact email	alex.vonkriegsheim@ucd.ie
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/2022/11/PXD037464

PRIDE project URI

• PRIDE
  1. PXD037464
     1. Label: PRIDE project
     2. Name: Dynamic partitioning of branched-chain amino acids- derived nitrogen supports renal cancer progression