Collective amoeboid migration of cancer cell clusters by polarised jiggling
Diane-Laure Pagès (Institut Gustave Roussy)
Winner of the PhysBio2021 best short talk award
Migration is a key step in many biological processes, including the metastatic progression of cancers which accounts for most patient’s deaths. As far as we know, cell locomotion occurs through three distinct mechanisms. In a few words, single cells can migrate via two modes, mesenchymal (adhesive, traction-based) or amoeboid (non-adhesive, propulsion-based). Cell cohorts are generally led by protrusive leaders, towing the collective through adhesion to the substrate.
We have been able to demonstrate the existence of an undescribed mode of collective migration. We study tumour cell clusters’ migration, transformed and non-transformed, in non-adherent microfabricated channels. This collective migration is independent of focal-adhesions and traction but is dependent on integrin-mediated friction to the substrate. Moreover, cell clusters display an actomyosin cortex that is polarised to the rear of clusters, proportionally to migration speed. Inhibiting ROCK and myosin activity decreases migration, while optogenetic activation of RhoA dictates directionality, demonstrating that this migration relies on actomyosin contractility [2]. However, such migration is not driven by a sustained cell or myosin flow. Instead, we observed fluctuating cell and myosin displacements that are correlated with clusters’ speed. We then demonstrate analytically that, together with friction with the substrate and myosin polarisation, this behaviour leads to migration. Our results suggest that cell clusters can use a unique mode of collective migration, based on “polarised jiggling”, that may explain the metastatic potential of these tumour intermediates. We call this new mode of migration “collective amoeboid migration”, by analogy with single cell amoeboid migration.
1. Zajac, O. et al. Tumour spheres with inverted polarity drive the formation of peritoneal metastases in patients with hypermethylated colorectal carcinomas. Nat. Cell Biol. 1 (2018). doi:10.1038/s41556-017-0027-6
2. Pagès, D.-L. et al. Cell clusters adopt a collective amoeboid mode of migration in confined non-adhesive environments. bioRxiv 2020.05.28.106203 (2020) doi:10.1101/2020.05.28.106203.