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The Pleiotropic Effects of Glutamine Metabolism in Cancer
Open AccessReview

Starve Cancer Cells of Glutamine: Break the Spell or Make a Hungry Monster?

by 1, 1,2 and 1,2,*
1
Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA
2
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(6), 804; https://doi.org/10.3390/cancers11060804
Received: 3 May 2019 / Revised: 4 June 2019 / Accepted: 6 June 2019 / Published: 11 June 2019
(This article belongs to the Special Issue Metabolic Reprogramming and Vulnerabilities in Cancer)
Distinct from normal differentiated tissues, cancer cells reprogram nutrient uptake and utilization to accommodate their elevated demands for biosynthesis and energy production. A hallmark of these types of reprogramming is the increased utilization of, and dependency on glutamine, a nonessential amino acid, for cancer cell growth and survival. It is well-accepted that glutamine is a versatile biosynthetic substrate in cancer cells beyond its role as a proteinogenic amino acid. In addition, accumulating evidence suggests that glutamine metabolism is regulated by many factors, including tumor origin, oncogene/tumor suppressor status, epigenetic alternations and tumor microenvironment. However, despite the emerging understanding of why cancer cells depend on glutamine for growth and survival, the contribution of glutamine metabolism to tumor progression under physiological conditions is still under investigation, partially because the level of glutamine in the tumor environment is often found low. Since targeting glutamine acquisition and utilization has been proposed to be a new therapeutic strategy in cancer, it is central to understand how tumor cells respond and adapt to glutamine starvation for optimized therapeutic intervention. In this review, we first summarize the diverse usage of glutamine to support cancer cell growth and survival, and then focus our discussion on the influence of other nutrients on cancer cell adaptation to glutamine starvation as well as its implication in cancer therapy. View Full-Text
Keywords: glutamine; biosynthesis; amino acid starvation; adaptation; asparagine; aspartate; arginine; glutaminase glutamine; biosynthesis; amino acid starvation; adaptation; asparagine; aspartate; arginine; glutaminase
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Jiang, J.; Srivastava, S.; Zhang, J. Starve Cancer Cells of Glutamine: Break the Spell or Make a Hungry Monster? Cancers 2019, 11, 804.

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Cancers, EISSN 2072-6694, Published by MDPI AG
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