Summary of Study ST002225
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
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
Study ID | ST002225 |
Study Title | Time sensitive contribution of the BCAA catabolism to the TCA cycle carbons in HK2, 786-O, OS-RC-2 and RFX-631 |
Study Summary | The objective of this experiment is to test the contribution of the branched chain amino acids catabolism to the carbons used in the TCA cycle. To test this hypothesis, we incubated human renal epithelial cells (HK2) and ccRCC cell lines (786-O, 786-M1A, OS-RC-2, OS-LM1, RFX-631) with 13C6-leucine and 13C6-isoleucine in Plasmax media for 10 mins, 1 hour and 3 hours. Data were generated from 5 independent cultures. This is Part 4 of the study and the experiment number is MS52. |
Institute | CECAD Research Center |
Last Name | Yang |
First Name | Ming |
Address | Joseph-Stelzmann-Straße 26, Köln, Koeln, 50931, Germany |
ming.yang@uni-koeln.de | |
Phone | 4922147884306 |
Submit Date | 2022-07-15 |
Raw Data Available | Yes |
Raw Data File Type(s) | raw(Thermo) |
Analysis Type Detail | LC-MS |
Release Date | 2022-08-03 |
Release Version | 1 |
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Project:
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 |