Abstract：
Metastasis is a multistep process by which cancer cells break away from their original location and spread to distant organs, and is responsible for the vast majority of cancer-related deaths. Preventing early metastatic dissemination would revolutionize the ability to fight cancer. Unfortunately, the relatively poor understanding of the molecular underpinnings of metastasis has hampered the development of effective anti-metastatic drugs. Although it is now accepted that disseminating tumour cells need to acquire multiple competencies to face the many obstacles they encounter before reaching their metastatic site(s), whether these competencies are acquired through an accumulation of metastasis-specific genetic alterations and/or non-genetic events is often debated. Here we review a growing body of literature highlighting the importance of both genetic and non-genetic reprogramming events during the metastatic cascade, and discuss how genetic and non-genetic processes act in concert to confer metastatic competencies. We also describe how recent technological advances, and in particular the advent of single-cell multi-omics and barcoding approaches, will help to better elucidate the cross-talk between genetic and non-genetic mechanisms of metastasis and ultimately inform innovative paths for the early detection and interception of this lethal process.
摘要：
转移是一个多步骤的过程，癌细胞脱离其原始位置并扩散到远处的器官，并且是绝大多数癌症相关死亡的原因。防止早期转移扩散将彻底改变抗击癌症的能力。不幸的是,对转移的分子基础的了解相对较少，这阻碍了有效抗转移药物的开发。虽然现在已经接受的是，传播肿瘤细胞需要获得多种能力来面对他们在到达转移部位之前遇到的许多障碍，这些能力是否通过转移特异性遗传改变和/或非遗传事件的积累而获得,通常存在争议.在这里，我们回顾了越来越多的文献，强调了在转移级联过程中遗传和非遗传重编程事件的重要性。并讨论遗传和非遗传过程如何协同作用以赋予转移能力。我们还描述了最近的技术进步，特别是单细胞多组学和条形码方法的出现，将有助于更好地阐明遗传和非遗传转移机制之间的交叉对话，并最终为早期发现和拦截这一致命过程提供创新途径。
