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| Status |
Public on Nov 10, 2022 |
| Title |
Dynamic partitioning of branched-chain amino acids- derived nitrogen supports renal cancer progression |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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.
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| |
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for HK2, 786-O and its metastatic derivatives 786-M1A
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| Contributor(s) |
Sciacovelli M, Dugourd A |
| Citation(s) |
36539415 |
| |
| Submission date |
Nov 03, 2022 |
| Last update date |
Feb 09, 2023 |
| Contact name |
Marco Sciacovelli |
| E-mail(s) |
M.Sciacovelli@liverpool.ac.uk
|
| Organization name |
University of Liverpool
|
| Street address |
Ashton Street, Sherrington Building
|
| City |
Liverpool |
| State/province |
Select State |
| ZIP/Postal code |
L693GE |
| Country |
United Kingdom |
| |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (9)
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| Relations |
| BioProject |
PRJNA897915 |
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