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Glutamine synthetase: a tumor suppressor in hepatocellular carcinoma? 
Weiwei Dai1 , Wei-Xing Zong2,*
1Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
2Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers-The State University of New Jersey, Piscataway, NJ 08854, USA
*Correspondence to:Wei-Xing Zong , Email:zongwx@pharmacy.rutgers.edu
J Mol Cell Biol, Volume 15, Issue 1, January 2023, mjad007,  https://doi.org/10.1093/jmcb/mjad007

Glutamine (Gln) is the most abundant free amino acid in the circulation. In addition to being a proteinogenic amino acid, it has multifaceted functions by serving as a nitrogen and carbon donor for the biosynthesis of essential metabolites, including nucleotides, hexosamines, and fatty acids, contributing to energy production via fueling the tricarboxylic acid cycle, regulating the redox balance, and stimulating mechanistic target of rapamycin complex 1 (mTORC1) (Altman et al., 2016Bott et al., 2019a). Cancer cells have a high demand for Gln to support their malignant growth, which can be met by an increased expression of Gln transporter to facilitate its uptake from the tumor microenvironment (Nicklin et al., 2009). In a situation where extracellular supply of Gln is limited, such as in poorly vascularized cancers including breast cancer and pancreatic ductal adenocarcinoma (PDAC), cell autonomous Gln synthesis kicks in.