CRUK/MRC Oxford Institute for Radiation Oncology, Oxford, United Kingdom.
Cancer Res. 2019 Apr 1;79(7):1274-1284. doi: 10.1158/0008-5472.CAN-18-2797. Epub 2019 Mar 20.
Posttranslational modifications of proteins have been implicated in pathogenesis of numerous diseases. Arginine deimination (also known as citrullination) has a principal role in progression of rheumatoid arthritis through generation of autoantibodies and exacerbation of the inflammatory response. Recently, multiple research groups provided solid evidence of citrullination being in control of cancer progression; however, there is no comprehensive overview of these findings. This article summarizes and critically reviews the influence of citrullination on different aspects of tumor biology, including (i) regulation of apoptosis and differentiation, (ii) promoting EMT and metastasis, and (iii) potential use of citrullinated antigens for immunotherapy. In addition, (iv) the role of citrullination as a cancer biomarker and (v) implication of neutrophil extracellular traps in tumorigenesis are discussed. In summary, current findings testify to the significance of arginine deimination in tumor biology and thus more basic and translational studies are needed to further explore this topic.
蛋白质的翻译后修饰与许多疾病的发病机制有关。精氨酸脱亚氨基（也称为瓜氨酸化）通过产生自身抗体和加重炎症反应，在类风湿关节炎的进展中起主要作用。最近，多个研究小组提供了确凿的证据表明瓜氨酸化控制着癌症的进展；然而，目前还没有对这些发现的全面综述。本文总结和批判性地回顾了瓜氨酸化对肿瘤生物学不同方面的影响，包括 (i) 凋亡和分化的调节，(ii) EMT 和转移的促进，以及 (iii) 瓜氨酸化抗原在免疫治疗中的潜在用途。此外，还讨论了 (iv) 瓜氨酸化作为癌症生物标志物的作用和 (v) 中性粒细胞胞外陷阱在肿瘤发生中的作用。总之，目前的研究结果证明了精氨酸脱亚氨基在肿瘤生物学中的重要性，因此需要更多的基础和转化研究来进一步探讨这一课题。
