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

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 cancer cell invasion depends on reducing actomyosin contractility at sites of cell-cell contact. When actomyosin is not down-regulated at cell-cell contacts migrating cells lose cohesion. We provide a novel molecular mechanism for this down-regulation. Depletion of Discoidin Domain Receptor 1 (DDR1) blocks collective cancer cell invasion in a range of 2D, 3D and ‘organotypic’ models. DDR1 co-ordinates the Par3/6 cell polarity complex through its C-terminus binding PDZ domains in Par3 and Par6. The DDR1/Par3/6 complex controls the localisation of RhoE to cell-cell contacts where it antagonizes ROCK-driven actomyosin contractility. Depletion of DDR1, Par3, Par6 or RhoE leads to increased actomyosin at cell-cell contacts, a loss of cell-cell cohesion and defective collective cell invasion.