Department of Otorhinolaryngology-Head and Neck Surgery, The Tumor Virology Program, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Department of Microbiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Lab Invest. 2018 Feb;98(2):258-268. doi: 10.1038/labinvest.2017.112. Epub 2017 Oct 16.
In cancer progression, metastasis is a major cause of poor survival of patients and can be targeted for therapeutic interventions. The first discovered metastatic-suppressor Nm23-H1 possesses nucleoside diphosphate kinase, histidine kinase, and DNase activity as a broad-spectrum enzyme. Recent advances in cancer metastasis have opened new ways for the development of therapeutic molecular approaches. In this review, we provide a summary of the current understanding of Nm23/NDPKs in the context of viral oncogenesis. We also focused on Nm23-H1-mediated cellular events with an emphasis on chromatin modifications. How Nm23-H1 modulates the activities of chromatin modifiers through interaction with Epstein-Barr virus-encoded oncogenic antigens and related crosstalks are discussed in the context of other oncogenic viruses. We also described the current understanding of the cellular and viral interactions of Nm23-H1 and their reference to transcription regulation and metastasis. Further, we summarized the recent therapeutic approaches targeting Nm23 and its potential links to pathways that can be exploited by oncogenic viruses.
在癌症进展中，转移是导致患者生存不良的主要原因，可以作为治疗干预的靶点。第一个发现的转移性抑制物 Nm23-H1 具有核苷二磷酸激酶、组氨酸激酶和 DNA 酶活性，是一种广谱酶。癌症转移的最新进展为治疗性分子方法的发展开辟了新途径。在这篇综述中，我们总结了 Nm23/NDPKs 在病毒致癌中的当前认识。我们还重点介绍了 Nm23-H1 介导的细胞事件，强调了染色质修饰。讨论了 Nm23-H1 通过与 Epstein-Barr 病毒编码的致癌抗原相互作用以及与其他致癌病毒的相关串扰来调节染色质修饰剂活性的方式。我们还描述了 Nm23-H1 的细胞和病毒相互作用及其对转录调节和转移的参考的当前理解。此外，我们总结了最近针对 Nm23 的治疗方法及其与致癌病毒可利用的途径的潜在联系。
