1 Institute of Biomedicine of Seville (IBiS), IBiS/"Virgen del Rocío" University Hospital/CSIC/University of Seville , Seville, Spain .
2 Department of Biochemistry and Molecular Biology, Maimonides Biomedical Research Institute of Córdoba (IMIBIC), University of Córdoba , Córdoba, Spain .
Antioxid Redox Signal. 2018 Nov 1;29(13):1312-1332. doi: 10.1089/ars.2017.7072. Epub 2017 Sep 22.
Nitric oxide (NO) is a physiopathological messenger generating different reactive nitrogen species (RNS) according to hypoxic, acidic and redox conditions. Recent Advances: RNS and reactive oxygen species (ROS) promote relevant post-translational modifications, such as nitrosation, nitration, and oxidation, in critical components of cell proliferation and death, epithelial-to-mesenchymal transition, and metastasis.
The pro- or antitumoral properties of NO are dependent on local concentration, redox state, cellular status, duration of exposure, and compartmentalization of NO generation. The increased expression of NO synthase has been associated with cancer progression. However, the experimental strategies leading to high intratumoral NO generation have been shown to exert antitumoral properties. The effect of NO and ROS on cell signaling is critically altered by factors modulating tumor progression such as oxygen content, metabolism, and inflammatory response. The review describes the alteration of key components involved in cell survival and death, metabolism, and metastasis induced by RNS- and ROS-related post-translational modifications.
The identification of the molecular targets affected by nitrosation, nitration, and oxidation, as well as their interactions with other post-translational modifications, will improve the understanding on the complex signaling and cell fate decision in cancer. The therapeutic NO-based strategies have to address the complex crosstalk among NO and ROS with regard to critical components affecting tumor cell survival, metabolism, and metastasis in the progression of cancer, as well as close interaction with ionizing radiation and chemotherapy.
一氧化氮 (NO) 是一种生理病理信使，根据缺氧、酸性和氧化还原条件产生不同的活性氮物种 (RNS)。
活性氮和活性氧 (ROS) 促进细胞增殖和死亡、上皮间质转化和转移等关键成分的相关翻译后修饰，如硝化、硝化和氧化。
NO 的促肿瘤或抗肿瘤特性取决于局部浓度、氧化还原状态、细胞状态、暴露时间和 NO 生成的区室化。NO 合酶的表达增加与癌症进展有关。然而，已经表明导致肿瘤内高 NO 生成的实验策略具有抗肿瘤特性。调节肿瘤进展的因素（如氧含量、代谢和炎症反应）会严重改变 NO 和 ROS 对细胞信号转导的影响。
综述描述了 RNS 和 ROS 相关翻译后修饰诱导的细胞存活和死亡、代谢和转移的关键成分的改变。
鉴定受硝化、硝化和氧化影响的分子靶标及其与其他翻译后修饰的相互作用，将提高对癌症中复杂信号转导和细胞命运决定的理解。基于 NO 的治疗策略必须解决 NO 和 ROS 之间的复杂串扰，以及它们与电离辐射和化疗的相互作用，以解决影响肿瘤细胞存活、代谢和转移的关键成分在癌症进展中的问题。
