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Open AccessJournal ArticleDOI

Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer.

Ralph J. DeBerardinis, +1 more
- 21 Jan 2010 - 
- Vol. 29, Iss: 3, pp 313-324
TLDR
The protean roles of glutamine in cancer are reviewed, both in the direct support of tumor growth and in mediating some of the complex effects on whole-body metabolism that are characteristic of tumor progression.
Abstract
Several decades of research have sought to characterize tumor cell metabolism in the hope that tumor-specific activities can be exploited to treat cancer. Having originated from Warburg's seminal observation of aerobic glycolysis in tumor cells, most of this attention has focused on glucose metabolism. However, since the 1950s cancer biologists have also recognized the importance of glutamine (Q) as a tumor nutrient. Glutamine contributes to essentially every core metabolic task of proliferating tumor cells: it participates in bioenergetics, supports cell defenses against oxidative stress and complements glucose metabolism in the production of macromolecules. The interest in glutamine metabolism has been heightened further by the recent findings that c-myc controls glutamine uptake and degradation, and that glutamine itself exerts influence over a number of signaling pathways that contribute to tumor growth. These observations are stimulating a renewed effort to understand the regulation of glutamine metabolism in tumors and to develop strategies to target glutamine metabolism in cancer. In this study we review the protean roles of glutamine in cancer, both in the direct support of tumor growth and in mediating some of the complex effects on whole-body metabolism that are characteristic of tumor progression.

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Citations
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Journal ArticleDOI

Otto Warburg's contributions to current concepts of cancer metabolism

TL;DR: Otto Warburg's observations are re-examine in relation to the current concepts of cancer metabolism as being intimately linked to alterations of mitochondrial DNA, oncogenes and tumour suppressors, and thus readily exploitable for cancer therapy.
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Aerobic Glycolysis: Meeting the Metabolic Requirements of Cell Proliferation

TL;DR: In this paper, the authors provide a detailed accounting of the biosynthetic requirements to construct a new cell and illustrate the importance of glycolysis in providing carbons to generate biomass.
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Glutamine supports pancreatic cancer growth through a Kras-regulated metabolic pathway

TL;DR: The identification of a non-canonical pathway of glutamine use in human pancreatic ductal adenocarcinoma (PDAC) cells is reported and it is established that the reprogramming of glutamines metabolism is mediated by oncogenic KRAS, the signature genetic alteration in PDAC, through the transcriptional upregulation and repression of key metabolic enzymes in this pathway.
Journal ArticleDOI

Glutamine addiction: a new therapeutic target in cancer.

TL;DR: In many cancer cells, glutamine is the primary mitochondrial substrate and is required for maintenance of mitochondrial membrane potential and integrity and for support of the NADPH production needed for redox control and macromolecular synthesis.
Journal ArticleDOI

From Krebs to clinic: glutamine metabolism to cancer therapy.

TL;DR: An updated overview of glutamine metabolism and its involvement in tumorigenesis in vitro and in vivo is provided, and the recent potential applications of basic science discoveries in the clinical setting are explored.
References
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Journal ArticleDOI

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Journal ArticleDOI

Beyond aerobic glycolysis : Transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis

TL;DR: Transformed cells exhibit a high rate of glutamine consumption that cannot be explained by the nitrogen demand imposed by nucleotide synthesis or maintenance of nonessential amino acid pools, and glutamine metabolism provides a carbon source that facilitates the cell's ability to use glucose-derived carbon and TCA cycle intermediates as biosynthetic precursors.
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