Summary of project PR001418
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001418. The data can be accessed directly via it's Project DOI: 10.21228/M8F409 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001418 |
| Project DOI: | doi: 10.21228/M8F409 |
| Project Title: | Dynamic partitioning of branched-chain amino acids-derived nitrogen supports renal cancer progression |
| Project 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 novel mechanism of metabolic flexibility occurring during ccRCC progression, paving the way for the development of novel stage-specific therapies. |
| Institute: | CECAD Research Center, University Hospital Cologne |
| Last Name: | Yang |
| First Name: | Ming |
| Address: | Joseph-Stelzmann-Straße 26, CECAD Research Center, Köln, Koeln, 50931, Germany |
| Email: | ming.yang@uni-koeln.de |
| Phone: | +4922147884306 |
Summary of all studies in project PR001418
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002220 | Catabolism of branched-chain amino acids (BCAAs) in renal cells HK2 and 786-O | Homo sapiens | CECAD Research Center | MS | 2022-08-03 | 1 | 20 | Uploaded data (2G)* |
| ST002221 | Glutaminolysis contribution to the carbon backbone of aspartate through ATP Citrate Lyase (ACLY) in ccRCC | Homo sapiens | CECAD Research Center | MS | 2022-08-03 | 1 | 45 | Uploaded data (8G)* |
| ST002222 | Glutaminolysis contribution to the carbon backbone of aspartate and glutamate in ccRCC | Homo sapiens | CECAD Research Center | MS | 2022-08-03 | 1 | 60 | Uploaded data (10.7G)* |
| ST002223 | Metabolic profiling of mouse tissues and tissue interstitial fluids | Mus musculus | CECAD Research Center | MS | 2022-08-03 | 1 | 63 | Uploaded data (6.5G)* |
| ST002224 | Intracellular metabolic profile of renal cells cultured in Plasmax | Homo sapiens | CECAD Research Center | MS | 2022-08-03 | 1 | 48 | Uploaded data (4.6G)* |
| ST002225 | Time sensitive contribution of the BCAA catabolism to the TCA cycle carbons in HK2, 786-O, OS-RC-2 and RFX-631 | Homo sapiens | CECAD Research Center | MS | 2022-08-03 | 1 | 108 | Uploaded data (10.3G)* |
| ST002226 | Exometabolomics of HK2, 786-O cells cultured in Plasmax media | Homo sapiens | CECAD Research Center | MS | 2022-08-03 | 1 | 39 | Uploaded data (3.5G)* |
| ST002227 | Assessing the contribution of branched-chain amino acid (BCAA)-derived nitrogen to amino acid biosynthesis in renal cell lines HK2 and 786-O. | Homo sapiens | CECAD Research Center | MS | 2022-08-03 | 1 | 20 | Uploaded data (2G)* |
