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

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 am...

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Main Authors: Jie Jiang, Sankalp Srivastava, Ji Zhang
Format: Article
Language:English
Published: MDPI AG 2019-06-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/11/6/804
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author Jie Jiang
Sankalp Srivastava
Ji Zhang
author_facet Jie Jiang
Sankalp Srivastava
Ji Zhang
author_sort Jie Jiang
collection DOAJ
description 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.
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spelling doaj.art-9bd8a02d64a84163af83faab25b05cf12023-09-02T08:08:41ZengMDPI AGCancers2072-66942019-06-0111680410.3390/cancers11060804cancers11060804Starve Cancer Cells of Glutamine: Break the Spell or Make a Hungry Monster?Jie Jiang0Sankalp Srivastava1Ji Zhang2Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USAHerman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USAHerman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USADistinct 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.https://www.mdpi.com/2072-6694/11/6/804glutaminebiosynthesisamino acid starvationadaptationasparagineaspartatearginineglutaminase
spellingShingle Jie Jiang
Sankalp Srivastava
Ji Zhang
Starve Cancer Cells of Glutamine: Break the Spell or Make a Hungry Monster?
Cancers
glutamine
biosynthesis
amino acid starvation
adaptation
asparagine
aspartate
arginine
glutaminase
title Starve Cancer Cells of Glutamine: Break the Spell or Make a Hungry Monster?
title_full Starve Cancer Cells of Glutamine: Break the Spell or Make a Hungry Monster?
title_fullStr Starve Cancer Cells of Glutamine: Break the Spell or Make a Hungry Monster?
title_full_unstemmed Starve Cancer Cells of Glutamine: Break the Spell or Make a Hungry Monster?
title_short Starve Cancer Cells of Glutamine: Break the Spell or Make a Hungry Monster?
title_sort starve cancer cells of glutamine break the spell or make a hungry monster
topic glutamine
biosynthesis
amino acid starvation
adaptation
asparagine
aspartate
arginine
glutaminase
url https://www.mdpi.com/2072-6694/11/6/804
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