Related Experiment Video
Updated: Nov 18, 2025
Glutamine Flux Imaging Using Genetically Encoded Sensors
Published on: July 31, 2014
Glutamine Synthetase as a Therapeutic Target for Cancer Treatment
Go Woon Kim1, Dong Hoon Lee1, Yu Hyun Jeon1
1College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Korea.
Abstract:
The significance of glutamine in cancer metabolism has been extensively studied. Cancer cells consume an excessive amount of glutamine to facilitate rapid proliferation. Thus, glutamine depletion occurs in various cancer types, especially in poorly vascularized cancers. This makes glutamine synthetase (GS), the only enzyme responsible for de novo synthesizing glutamine, essential in cancer metabolism. In cancer, GS exhibits pro-tumoral features by synthesizing glutamine, supporting nucleotide synthesis. Furthermore, GS is highly expressed in the tumor microenvironment (TME) and provides glutamine to cancer cells, allowing cancer cells to maintain sufficient glutamine level for glutamine catabolism. Glutamine catabolism, the opposite reaction of glutamine synthesis by GS, is well known for supporting cancer cell proliferation via contributing biosynthesis of various essential molecules and energy production. Either glutamine anabolism or catabolism has a critical function in cancer metabolism depending on the complex nature and microenvironment of cancers. In this review, we focus on the role of GS in a variety of cancer types and microenvironments and highlight the mechanism of GS at the transcriptional and post-translational levels. Lastly, we discuss the therapeutic implications of targeting GS in cancer.
Insights
Glutamine synthetase (GS) is crucial for cancer growth by synthesizing glutamine, fueling proliferation. Targeting GS offers a promising therapeutic strategy for various cancers, especially those with limited blood supply.
Area of Science:
- Oncology
- Cancer Metabolism
- Biochemistry
Background:
- Cancer cells exhibit high glutamine consumption to support rapid proliferation.
- Glutamine depletion is common in cancers, particularly in poorly vascularized tumors.
- Glutamine synthetase (GS) is the primary enzyme for de novo glutamine synthesis and is vital in cancer metabolism.
Purpose of the Study:
- To review the multifaceted role of glutamine synthetase (GS) in diverse cancer types and microenvironments.
- To elucidate the mechanisms regulating GS at transcriptional and post-translational levels.
- To explore the therapeutic potential of targeting GS in cancer treatment.
Main Methods:
- Literature review focusing on glutamine synthetase in cancer metabolism.
- Analysis of GS expression and function in various tumor microenvironments (TME).
- Investigation of GS regulatory mechanisms, including transcriptional and post-translational modifications.
Main Results:
- GS plays a pro-tumoral role by synthesizing glutamine, supporting nucleotide synthesis and proliferation.
- High GS expression in the TME provides essential glutamine to cancer cells for catabolism.
- Both glutamine anabolism (synthesis) and catabolism are critical for cancer cell proliferation, depending on cancer type and microenvironment.
Conclusions:
- Glutamine synthetase is a key player in cancer metabolism, supporting tumor growth through glutamine synthesis.
- Understanding GS regulation at multiple levels is crucial for developing targeted cancer therapies.
- Targeting GS presents a viable therapeutic strategy for a range of cancers, warranting further investigation.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:23Abnormal Proliferation
02:38Mitogens and the Cell Cycle