Arginine dependence of tumor cells: targeting a chink in cancer's armor.
Arginine dependence of tumor cells: targeting a chink in cancer's armor.
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DOI：
10.1038/onc.2016.37
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发表时间：
2016-09-22
期刊：
影响因子：
8
通讯作者：
Fukumura D
中科院分区：
文献类型：
--
作者：
Patil MD;Bhaumik J;Babykutty S;Banerjee UC;Fukumura D
精氨酸是 20 种最常见的天然氨基酸之一，在细胞生理学中发挥着关键作用，因为它参与许多细胞代谢和信号传导途径。肿瘤细胞和正常细胞对精氨酸的依赖性是不同的。由于精氨酸琥珀酸合成酶和/或鸟氨酸转氨甲酰酶的表达降低，几种类型的肿瘤是精氨酸营养缺陷型的。精氨酸的缺乏利用了这些肿瘤细胞的显着脆弱性并导致它们迅速死亡。因此，酶介导的精氨酸消耗是选择性破坏肿瘤细胞的潜在策略。精氨酸酶、精氨酸脱亚胺酶和精氨酸脱羧酶是可用于精氨酸剥夺疗法的潜在酶。这些精氨酸分解代谢酶不仅可以减少肿瘤生长，还使它们容易受到同时施用的抗癌治疗的影响。大多数这些酶目前正在临床研究中，如果成功，将有可能被推进为抗癌模式。
Arginine, one among the 20 most common natural amino acids, has a pivotal role in cellular physiology as it is being involved in numerous cellular metabolic and signaling pathways. Dependence on arginine is diverse for both tumor and normal cells. Because of decreased expression of argininosuccinate synthetase and/or ornithine transcarbamoylase, several types of tumor are auxotrophic for arginine. Deprivation of arginine exploits a significant vulnerability of these tumor cells and leads to their rapid demise. Hence, enzyme-mediated arginine depletion is a potential strategy for the selective destruction of tumor cells. Arginase, arginine deiminase and arginine decarboxylase are potential enzymes that may be used for arginine deprivation therapy. These arginine catabolizing enzymes not only reduce tumor growth but also make them susceptible to concomitantly administered anti-cancer therapeutics. Most of these enzymes are currently under clinical investigations and if successful will potentially be advanced as anti-cancer modalities.