Collective cell migration requires suppression of actomyosin at cell–cell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6

A complex containing the Par3/6 polarity proteins and the matrix receptor DDR1 modulates migration by downregulating cortical actomyosin contractility. Collective cell migration occurs in a range of contexts: cancer cells frequently invade in cohorts while retaining cell–cell junctions. Here we show that collective invasion by cancer cells depends on decreasing actomyosin contractility at sites of cell–cell contact. When actomyosin is not downregulated at cell–cell contacts, migrating cells lose cohesion. We provide a molecular mechanism for this downregulation. Depletion of discoidin domain receptor 1 (DDR1) blocks collective cancer-cell invasion in a range of two-dimensional, three-dimensional and 'organotypic' models. DDR1 coordinates the Par3/Par6 cell-polarity complex through its carboxy terminus, binding PDZ domains in Par3 and Par6. The DDR1–Par3/Par6 complex controls the localization of RhoE to cell–cell contacts, where it antagonizes ROCK-driven actomyosin contractility. Depletion of DDR1, Par3, Par6 or RhoE leads to increased actomyosin contactility at cell–cell contacts, a loss of cell–cell cohesion and defective collective cell invasion.