转移是癌症患者死亡的主要原因，但仍然存在未解决的问题。传统上，转移扩散与肌动蛋白驱动的细胞运动有关。然而，癌细胞的运动经常不能严格地与测量到的肌动蛋白力相匹配。本研究发现了一种由动力蛋白产生的力推动的转移运动的补充机制。这些力产生于一个不可伸展的微管网络中，并驱动迁移的癌细胞沿仿生胶原纤维进行持续的接触引导。同时，结果还显示在与由微米水凝胶颗粒（微凝胶）组成的空间约束颗粒水凝胶支架（GHS）形成的组织样腔道网络中进行侵袭性三维迁移时，由动力蛋白驱动的运动变得不可或缺。这些结果表明，动力蛋白介导的补充运动在传播转移性乳腺癌细胞时始终是必需的，并且在某些情况下足以实现目标。这些发现推进了对细胞运动机制的基础理解，并扩展了针对转移的临床靶点的范围。© 2023 Wiley-VCH GmbH出版的Advanced Science上发表的研究结果。

The principal cause of death in cancer patients is metastasis, which remains an unresolved problem. Conventionally, metastatic dissemination is linked to actomyosin-driven cell locomotion. However, the locomotion of cancer cells often does not strictly line up with the measured actomyosin forces. Here, a complementary mechanism of metastatic locomotion powered by dynein-generated forces is identified. These forces arise within a non-stretchable microtubule network and drive persistent contact guidance of migrating cancer cells along the biomimetic collagen fibers. It is also shown that the dynein-powered locomotion becomes indispensable during invasive 3D migration within a tissue-like luminal network formed by spatially confining granular hydrogel scaffolds (GHS) made up of microscale hydrogel particles (microgels). These results indicate that the complementary motricity mediated by dynein is always necessary and, in certain instances, sufficient for disseminating metastatic breast cancer cells. These findings advance the fundamental understanding of cell locomotion mechanisms and expand the spectrum of clinical targets against metastasis.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.