Plasticity of cancer invasion and metastasis depends on the ability of cancer cells to switch between collective and single-cell dissemination, controlled by cadherin-mediated cell–cell junctions. In clinical samples, E-cadherin-expressing and -deficient tumours both invade collectively and metastasize equally, implicating additional mechanisms controlling cell–cell cooperation and individualization. Here, using spatially defined organotypic culture, intravital microscopy of mammary tumours in mice and in silico modelling, we identify cell density regulation by three-dimensional tissue boundaries to physically control collective movement irrespective of the composition and stability of cell–cell junctions. Deregulation of adherens junctions by downregulation of E-cadherin and p120-catenin resulted in a transition from coordinated to uncoordinated collective movement along extracellular boundaries, whereas single-cell escape depended on locally free tissue space. These results indicate that cadherins and extracellular matrix confinement cooperate to determine unjamming transitions and stepwise epithelial fluidization towards, ultimately, cell individualization.

癌症侵袭和转移的可塑性取决于癌细胞在集体传播和单细胞传播之间切换的能力，由钙粘蛋白介导的细胞间连接控制。在临床样本中，表达 E-钙粘蛋白的肿瘤和缺乏 E-钙粘蛋白的肿瘤均同时集体侵袭和转移，这意味着控制细胞间合作和个体化的其他机制。在这里，利用空间定义的器官型培养、小鼠乳腺肿瘤的活体显微镜和计算机建模，我们通过三维组织边界识别细胞密度调节，以物理控制集体运动，而不管细胞-细胞连接的组成和稳定性如何。通过下调 E-钙粘蛋白和 p120-连环蛋白来放松粘附连接，导致沿细胞外边界从协调集体运动转变为不协调集体运动，而单细胞逃逸则依赖于局部自由组织空间。这些结果表明钙粘蛋白和细胞外基质限制合作确定无干扰转变和逐步上皮流化，最终实现细胞个体化。