Arginine and the metabolic regulation of nitric oxide synthesis in cancer.
Arginine and the metabolic regulation of nitric oxide synthesis in cancer.
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DOI：
10.1242/dmm.033332
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发表时间：
2018-08-06
影响因子：
4.3
通讯作者：
Erez A
中科院分区：
文献类型：
--
作者：
Keshet R;Erez A
一氧化氮（NO）是一种信号分子，在多种生物过程中发挥重要作用，其失调与多种疾病的发病有关。在癌症中，NO具有广泛的，有时是双重的作用；它参与癌症的发生和发展，但也限制癌症的增殖和侵袭，并有助于抗肿瘤免疫反应。一氧化氮在一系列细胞过程中的重要性体现在其在多个水平上的严格空间和剂量控制，包括其转录、翻译后和代谢调节。在这篇综述中，我们主要关注一氧化氮通过其前体精氨酸的合成和可用性来调节，并讨论这种代谢调节对癌症生物学和治疗的意义。尽管一氧化氮在癌症发病机制中的作用已经确立，但一氧化氮相关癌症治疗的实施仍然有限，这可能是由于以细胞和剂量特异性的方式靶向和诱导其保护功能的挑战。因此，更好地了解精氨酸如何调节癌症中NO的产生，可能有助于开发针对这一关键代谢途径以及参与NO产生的其他代谢途径的抗癌药物。摘要：本文综述了精氨酸的合成和利用对NO水平的调节，以及这种代谢调节对癌症生物学和治疗的意义。
Nitric oxide (NO) is a signaling molecule that plays important roles in diverse biological processes and thus its dysregulation is involved in the pathogenesis of various disorders. In cancer, NO has broad and sometimes dichotomous roles; it is involved in cancer initiation and progression, but also restricts cancer proliferation and invasion, and contributes to the anti-tumor immune response. The importance of NO in a range of cellular processes is exemplified by its tight spatial and dosage control at multiple levels, including via its transcriptional, post-translational and metabolic regulation. In this Review, we focus on the regulation of NO via the synthesis and availability of its precursor, arginine, and discuss the implications of this metabolic regulation for cancer biology and therapy. Despite the established contribution of NO to cancer pathogenesis, the implementation of NO-related cancer therapeutics remains limited, likely due to the challenge of targeting and inducing its protective functions in a cell- and dosage-specific manner. A better understanding of how arginine regulates the production of NO in cancer might thus support the development of anti-cancer drugs that target this key metabolic pathway, and other metabolic pathways involved in NO production. Summary: In this Review, the authors focus on the regulation of NO levels by the synthesis and availability of arginine, and on the implications of this metabolic regulation to cancer biology and therapy.
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