An EpCAM/Trop2 mechanostat differentially regulates individual and collective migration of human carcinoma cells

Author:

Aslemarz Azam,Kaufmann Marie-Fagotto,Ruppel Artur,Balland Martial,Lasko Paul,Fagotto François

Abstract

AbstractEpCAM is well-known as a carcinoma associated cell surface protein, but its potential role in cancer metastasis remains unclear. It is known, however, to downregulate myosin-dependent contractility, a key parameter involved in cell adhesion and migration. We investigate here the morphogenetic impact of EpCAM levels in epithelial breast cancer cells, using spheroids of MCF7 cells as in vitro model of pre-metastatic cells. We find that EpCAM represses collective migration, while it stimulates single cell migration. MCF7, as most epithelial cells, also express Trop2, a close relative of EpCAM. Intriguingly, Trop2 depletion led to the exact opposite phenotype from EpCAM depletion in terms of single cell migration, tissue cohesiveness and collective migration. Using a combination of cell biological and biophysical approaches, we show that EpCAM and Trop2 both contribute to moderate cell contractility. Yet, as a result of subtle differences in their cellular distribution, they differentially impact on the balance of local cortical contractility, which is sufficient to account for the opposite migratory phenotypes. Our study reveals that the EpCAM-Trop2 pair acts as a mechanostat that, by finely tuning local cortical tension, controls tissue cohesiveness and distinct modes of migration.

Publisher

Cold Spring Harbor Laboratory

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