An EpCAM/Trop2 mechanostat differentially regulates collective behaviour of human carcinoma cells

EpCAM and its close relative Trop2 are well-known cell surface markers of carcinoma, but their potential role in cancer metastasis remains unclear. They are known, however, to downregulate myosin-dependent contractility, a key parameter involved in adhesion and migration. Here, we investigate the morphogenetic impact of the high EpCAM and Trop2 levels typically found in epithelial breast cancer cells, using spheroids of MCF7 cells as an in vitro model. Intriguingly, EpCAM depletion stimulated spheroid cohesive spreading, while Trop2 depletion had the opposite effect. Combining cell biological and biophysical approaches, we demonstrate that while EpCAM and Trop2 both contribute to moderate cell contractility, their depletions differentially impact on the process of "wetting" a substrate, here both matrix and neighboring cells, by affecting the balance of cortical tension at cell and tissue interfaces. These distinct phenotypes can be explained by partial enrichment at specific interfaces. Our data are consistent with the EpCAM-Trop2 pair acting as a mechanostat that tunes adhesive and migratory behaviours.