Metastasis remains the greatest challenge in the clinical management of cancer. Cell motility is a fundamental and ancient cellular behaviour that contributes to metastasis and is conserved in simple organisms. In this Review, we evaluate insights relevant to human cancer that are derived from the study of cell motility in non-mammalian model organisms. Dictyostelium discoideum, Caenorhabditis elegans, Drosophila melanogaster and Danio rerio permit direct observation of cells moving in complex native environments and lend themselves to large-scale genetic and pharmacological screening. We highlight insights derived from each of these organisms, including the detailed signalling network that governs chemotaxis towards chemokines; a novel mechanism of basement membrane invasion; the positive role of E-cadherin in collective direction-sensing; the identification and optimization of kinase inhibitors for metastatic thyroid cancer on the basis of work in flies; and the value of zebrafish for live imaging, especially of vascular remodelling and interactions between tumour cells and host tissues. While the motility of tumour cells and certain host cells promotes metastatic spread, the motility of tumour-reactive T cells likely increases their antitumour effects. Therefore, it is important to elucidate the mechanisms underlying all types of cell motility, with the ultimate goal of identifying combination therapies that will increase the motility of beneficial cells and block the spread of harmful cells.

转移仍然是癌症临床管理中的最大挑战。细胞运动性是一种基本的古老的细胞行为，有助于转移，在简单的生物体中是保守的。在这篇综述中，我们评估了与人类癌症相关的见解，这些见解源于对非哺乳动物模型生物中细胞运动性的研究。盘基网柄菌，秀丽隐杆线虫，黑腹果蝇和雷氏达尼奥可以直接观察在复杂的自然环境中移动的细胞，并适合进行大规模的遗传和药理学筛选。我们重点介绍了从这些生物中的每一种获得的见解，包括控制趋化因子趋化性的详细信号网络；基底膜侵袭的新机制；E-钙粘着蛋白在集体方向感测中的积极作用；在果蝇工作的基础上鉴定和优化转移性甲状腺癌激酶抑制剂；以及斑马鱼在实时成像中的价值，尤其是在血管重塑以及肿瘤细胞与宿主组织之间的相互作用方面。肿瘤细胞和某些宿主细胞的运动促进转移扩散，而肿瘤反应性T细胞的运动可能会增强其抗肿瘤作用。所以，