Cell clusters adopt a collective amoeboid mode of migration in confined non-adhesive environments

Abstract

Cell migration is essential to most living organisms. Single cell migration involves two distinct mechanisms, either a focal adhesion- and traction-dependent mesenchymal motility or an adhesion-independent but contractility-driven propulsive amoeboid locomotion. Cohesive migration of a group of cells, also called collective cell migration, has been only described as an adhesion- and traction-dependent mode of locomotion where the driving forces are mostly exerted at the front by leader cells. Here, by studying primary cancer specimens and cell lines from colorectal cancer, we demonstrate the existence of a second mode of collective migration which does not require adhesion to the surroundings and relies on a polarised supracellular contractility. Cell clusters confined into non-adhesive microchannels migrate in a rounded morphology, independently of the formation of focal adhesions or protruding leader cells, and lacking internal flow of cells, ruling-out classical traction-driven collective migration. Like single cells migrating in an amoeboid fashion, the clusters display a supracellular actin cortex with myosin II enriched at the rear. Using pharmacological inhibitors and optogenetics, we show that this polarised actomyosin activity powers migration and propels the clusters. This new mode of migration, that we named collective amoeboid, could be enabled by intrinsic or extrinsic neoplasic features to enable the metastatic spread of cancers. One Sentence SummaryClusters organise as polarised and contractile super-cells to migrate without adhesion.