Summary of Study ST002220

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.

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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.

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Study IDST002220
Study TitleCatabolism of branched-chain amino acids (BCAAs) in renal cells HK2 and 786-O
Study SummaryThe objective of this experiment is to compare the catabolism of branched-chain amino acids (BCAAs) in human renal epithelial cell line HK2 versus ccRCC cell lines 786-O, 786-M1A and 786-M2A using 13C6-labelled leucine and isoleucine stable isotope tracers. To this end, we incubated the above cell lines with 13C6-leucine and 13C6-isoleucine in Plasmax media for 27h. Data were generated from 5 independent cultures. This is Part I of the study and the experimental number is MS42.
Institute
CECAD Research Center
Last NameYang
First NameMing
AddressJoseph-Stelzmann-Straße 26, CECAD Research Center, Köln, Koeln, 50931, Germany
Emailming.yang@uni-koeln.de
Phone+4922147884306
Submit Date2022-07-15
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2022-08-03
Release Version1
Ming Yang Ming Yang
https://dx.doi.org/10.21228/M8F409
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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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
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