Glutamine synthetase as a therapeutic target for cancer treatment

Go Woon Kim, Dong Hoon Lee, Yu Hyun Jeon, Jung Yoo, So Yeon Kim, Sang Wu Lee, Ha Young Cho, So Hee Kwon

Research output: Contribution to journalReview articlepeer-review

24 Citations (Scopus)


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 glu-tamine 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 microenviron-ments and highlight the mechanism of GS at the transcriptional and post‐translational levels. Lastly, we discuss the therapeutic implications of targeting GS in cancer.

Original languageEnglish
Article number1701
Pages (from-to)1-17
Number of pages17
JournalInternational journal of molecular sciences
Issue number4
Publication statusPublished - 2021 Feb 2

Bibliographical note

Funding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2018R1A6A1A03023718, 2019R1A2C1008619, 2019R1I1A1A01058601, and 2019H1A2A1076925).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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