Collective cell migration plasticity in patient-derived digestive cancer organoids is dictated by environment sensing and contractility

The metastatic dissemination of individual cells or cell collectives is a decisive step in the progression of cancers. Migrating single cells dynamically switch between mesenchymal traction-based and amoeboid propulsion-based modes of migration in a mechanism named plasticity. Collective cell migration has mainly been described as a traction-dependent mode of locomotion. While a propulsive collective cell migration has recently been reported, we question whether cell clusters are also endowed with plasticity. Here, we report that patient-derived digestive cancer organoids exhibit a preferred mode of migration but transition to the alternate strategy to adapt to external stimuli or to the manipulation of intrinsic determinants. We show that the tumor cell cluster plasticity observed in vitro ensures efficient metastatic seeding in a murine model of peritoneal carcinomatosis. These findings reveal an adaptive mechanism at play during tumor invasion that must further be decrypted to enable the design of therapeutic strategies halting metastatic progression.