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PXD037464-1

PXD037464 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDynamic partitioning of branched-chain amino acids- derived nitrogen supports renal cancer progression
DescriptionMetabolic 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.
HostingRepositoryPRIDE
AnnounceDate2022-11-09
AnnouncementXMLSubmission_2022-11-09_07:26:45.805.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAlexvon kriegsheim
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-10-15 14:38:34ID requested
12022-11-09 07:26:46announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Metabolism, Renal Cancer
Contact List
Alex vonKriegsheim
contact affiliationUniversity of Edinburgh
contact emailavonkri@ed.ac.uk
lab head
Alexvon kriegsheim
contact affiliationUniversity of Edinburgh
contact emailalex.vonkriegsheim@ucd.ie
dataset submitter
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Dataset FTP location
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