Salimian Rizi Bahar, Achreja Abhinav, Nagrath Deepak
Agilent Technologies, Lexington, Massachusetts, USA; These authors contributed equally to this work.
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan, USA; These authors contributed equally to this work.
Trends Cancer. 2017 Sep;3(9):659-672. doi: 10.1016/j.trecan.2017.07.005. Epub 2017 Aug 18.
Nitric oxide (NO) is a signaling molecule with pleiotropic physiological roles in normal cells and pathophysiological roles in cancer. NO synthetase expression and NO synthesis are linked to altered metabolism, neoplasticity, invasiveness, chemoresistance, immune evasion, and ultimately to poor prognosis of cancer patients. Exogenous NO in the microenvironment facilitates paracrine signaling, mediates immune responses, and triggers angiogenesis. NO regulates posttranslational protein modifications, S-nitrosation, and genome-wide epigenetic modifications that can have both tumor-promoting and tumor-suppressing effects. We review mechanisms that link NO to cancer hallmarks, with a perspective of co-targeting NO metabolism with first-line therapies for improved outcome. We highlight the need for quantitative flux analysis to study NO in tumors.
一氧化氮（NO）是一种信号分子，在正常细胞中具有多效性生理作用，在癌症中具有病理生理作用。NO合酶表达和NO合成与代谢改变、肿瘤形成、侵袭性、化疗耐药性、免疫逃逸相关，最终与癌症患者的不良预后相关。微环境中的外源性NO促进旁分泌信号传导，介导免疫反应，并触发血管生成。NO调节蛋白质翻译后修饰、S-亚硝基化和全基因组表观遗传修饰，这些修饰可能具有促肿瘤和抑肿瘤作用。我们综述了将NO与癌症标志联系起来的机制，并展望了将NO代谢与一线治疗联合靶向以改善治疗效果。我们强调了进行定量通量分析以研究肿瘤中NO的必要性。
