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

Nature cell biology (2010-12-21)
Cristina Hidalgo-Carcedo, Steven Hooper, Shahid I Chaudhry, Peter Williamson, Kevin Harrington, Birgit Leitinger, Erik Sahai
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Partitioning-defective 3 Antibody, Upstate®, from rabbit
Millipore
Protein G Sepharose®, Fast Flow, recombinant, expressed in E. coli, aqueous ethanol suspension