Glutamine Synthetase: Localization Dictates Outcome.
Glutamine Synthetase: Localization Dictates Outcome.
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DOI：
10.3390/genes9020108
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发表时间：
2018-02-19
期刊：
影响因子：
3.5
通讯作者：
Menga A
中科院分区：
文献类型：
--
作者：
Castegna A;Menga A
谷氨酰胺合成酶（GS）是一种依赖三磷酸腺苷（ATP）的酶，它通过将铵与谷氨酸缩合来催化谷氨酰胺的合成。在循环系统中，谷氨酰胺将氨从肌肉和大脑运输到肾脏和肝脏。在大脑中，谷氨酰胺合成酶活性的降低被认为是神经退行性疾病中神经毒性的一种介导机制。在癌症中，谷氨酰胺合成与分解代谢之间的微妙平衡是一个关键事件。体外证据（在某些情况下在体内得到证实）表明，癌细胞中谷氨酰胺合成酶活性的降低与更具侵袭性和攻击性的表型相关。然而，已知谷氨酰胺合成酶在肿瘤微环境的细胞（如成纤维细胞、脂肪细胞和免疫细胞）中高度表达，它们合成谷氨酰胺的能力是获得促肿瘤表型的原因。这为肿瘤微环境的复杂情况打开了一扇新的窗口，其中谷氨酰胺消耗与谷氨酰胺合成的平衡影响细胞功能。由于谷氨酰胺合成酶的表达对谷氨酰胺缺乏有反应，癌细胞中由于缺乏谷氨酰胺合成酶而导致的较低的谷氨酰胺合成能力可能会对基质细胞施加代谢压力。这一事件可能促使基质细胞趋向于谷氨酰胺合成酶高表达/促肿瘤表型。当涉及基质细胞时，谷氨酰胺合成酶的表达可能具有“不良”意义，以至于抑制谷氨酰胺合成酶可能被视为一种针对癌症转移的可行策略。
Glutamine synthetase (GS) is the adenosine triphosphate (ATP)-dependent enzyme that catalyses the synthesis of glutamine by condensing ammonium to glutamate. In the circulatory system, glutamine carries ammonia from muscle and brain to the kidney and liver. In brain reduction of GS activity has been suggested as a mechanism mediating neurotoxicity in neurodegenerative disorders. In cancer, the delicate balance between glutamine synthesis and catabolism is a critical event. In vitro evidence, confirmed in vivo in some cases, suggests that reduced GS activity in cancer cells associates with a more invasive and aggressive phenotype. However, GS is known to be highly expressed in cells of the tumor microenvironment, such as fibroblasts, adipocytes and immune cells, and their ability to synthesize glutamine is responsible for the acquisition of protumoral phenotypes. This has opened a new window into the complex scenario of the tumor microenvironment, in which the balance of glutamine consumption versus glutamine synthesis influences cellular function. Since GS expression responds to glutamine starvation, a lower glutamine synthesizing power due to the absence of GS in cancer cells might apply a metabolic pressure on stromal cells. This event might push stroma towards a GS-high/protumoral phenotype. When referred to stromal cells, GS expression might acquire a ‘bad’ significance to the point that GS inhibition might be considered a conceivable strategy against cancer metastasis.
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影响因子：
11.2
作者：
Ehsanipour EA;Sheng X;Behan JW;Wang X;Butturini A;Avramis VI;Mittelman SD
通讯作者：
Mittelman SD
影响因子：
6.3
作者：
Dadsetan, Sherry;Kukolj, Eva;Waagepetersen, Helle S.
通讯作者：
Waagepetersen, Helle S.
影响因子：
7.4
作者：
Castegna, A;Aksenov, M;Butterfield, DA
通讯作者：
Butterfield, DA
影响因子：
4.4
作者：
Cooper, Arthur J. L.
通讯作者：
Cooper, Arthur J. L.
影响因子：
5
作者：
Chrétien, F;Vallat-Decouvelaere, AV;Gras, G
通讯作者：
Gras, G