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Glutamine Synthetase: Localization Dictates Outcome
Alessandra Castegna1,2, Alessio Menga3
1Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari 70125, Italy. alessandra.castegna@uniba.it.
Genes
|February 22, 2018
Summary
Glutamine synthetase (GS) in cancer cells may reduce invasiveness, but its presence in stromal cells promotes tumor growth. Inhibiting GS in stromal cells could be a strategy against cancer metastasis.
Area of Science:
- Biochemistry
- Oncology
- Cell Biology
Background:
- Glutamine synthetase (GS) synthesizes glutamine from glutamate and ammonium, crucial for ammonia transport and cellular metabolism.
- Reduced GS activity in the brain is linked to neurotoxicity in neurodegenerative diseases.
- GS plays a complex role in cancer, with reduced activity in cancer cells potentially correlating with aggressiveness, while high expression in tumor microenvironment cells supports protumoral phenotypes.
Purpose of the Study:
- To explore the dual role of Glutamine Synthetase (GS) in cancer cells versus the tumor microenvironment.
- To investigate the implications of GS expression levels on cancer cell invasiveness and tumor progression.
- To evaluate the potential of GS inhibition as a therapeutic strategy against cancer metastasis.
Main Methods:
- Review of in vitro and in vivo evidence regarding GS activity in cancer cells and stromal cells.
- Analysis of the metabolic interplay between cancer cells and the tumor microenvironment concerning glutamine synthesis and consumption.
- Examination of the correlation between GS expression in stromal cells and protumoral phenotypes.
Main Results:
- Reduced GS activity in cancer cells may be associated with a less invasive phenotype.
- High GS expression in tumor-associated stromal cells (fibroblasts, adipocytes, immune cells) contributes to protumoral phenotypes.
- Glutamine starvation in cancer cells can induce GS upregulation in stromal cells, potentially promoting a protumoral state.
Conclusions:
- The role of GS in cancer is context-dependent, differing between cancer cells and the tumor microenvironment.
- GS expression in stromal cells appears to have a detrimental role, promoting cancer progression and metastasis.
- Inhibiting GS in stromal cells presents a potential therapeutic avenue to combat cancer metastasis.
Keywords:
M2 macrophagesadipocytesbraincancerglutaminaseglutamineglutamine synthetaseimmunometabolismimmunosuppressivemetabolismMore Related Videos
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