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Metabolic Differences in Glutamine Utilization Lead to Metabolic Vulnerabilities in Prostate Cancer

Title
Metabolic Differences in Glutamine Utilization Lead to Metabolic Vulnerabilities in Prostate Cancer
Author
이영복
Keywords
GLYCOLYTIC METABOLISM; ABIRATERONE ACETATE; CELL-PROLIFERATION; CITRATE; LACTATE; PROTEIN; EXPRESSION; LEUKEMIA; PYRUVATE; SURVIVAL
Issue Date
2017-11
Publisher
NATURE PUBLISHING GROUP
Citation
SCIENTIFIC REPORTS, v. 7, Article no. 16159
Abstract
The new oncologic paradigm of precision medicine is focused on identifying metabolic, proteomic, transcriptomic and genomic variabilities in tumors that can be exploited to tailor treatments and improve patient outcomes. Metabolic changes are a hallmark of cancer, and inhibition of metabolic pathways is now a major strategy in medicinal chemistry for targeting cancers. However, non-invasive biomarkers to categorize metabolic subtypes are in short supply. The purpose of this study was to characterize the intracellular and extracellular metabolic profiles of four prostate cancer cell lines with varying degrees of aggressiveness. We observed metabolic differences between the aggressive prostate cancer cell line PC3 and the even more aggressive, metastatic subline PC3M assessed by hyperpolarized in vivo pyruvate studies, nuclear magnetic resonance spectroscopy, and carbon-13 feeding studies. On further examination of the differences between these two cell lines, we found increased glutamine utilization in the metastatic PC3M subline that led directly to sensitivity to glutaminase inhibitor CB839. Our study supports the theory that metastatic progression increases glutamine utilization and the inhibition of glutaminolysis could have clinical implications.
URI
https://www.nature.com/articles/s41598-017-16327-zhttp://repository.hanyang.ac.kr/handle/20.500.11754/116141
ISSN
2045-2322
DOI
10.1038/s41598-017-16327-z
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > BIONANOTECHNOLOGY(바이오나노학과) > Articles
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