Collective cell migration requires suppression of actomyosin at cell-cell contacts mediated by DDR1 and the cell...

Area of Science:

• Cell Biology
• Cancer Research
• Molecular Biology

Background:

• Collective cell migration is vital in cancer invasion, where cells move in groups while maintaining connections.
• Understanding the molecular mechanisms regulating collective invasion is crucial for developing targeted therapies.

Purpose of the Study:

• To elucidate the molecular mechanism by which cancer cells maintain collective invasion.
• To identify key regulators of actomyosin contractility at cell-cell contacts during collective migration.

Main Methods:

• Investigated collective cancer cell invasion in 2D, 3D, and organotypic models.
• Utilized depletion studies of discoidin domain receptor 1 (DDR1) and associated proteins.
• Analyzed actomyosin contractility, cell-cell cohesion, and cell polarity.

Main Results:

• Decreased actomyosin contractility at cell-cell contacts is essential for collective cancer cell invasion.
• Depletion of DDR1 disrupts collective invasion by increasing contractility and reducing cell cohesion.
• DDR1 coordinates the Par3/Par6 polarity complex to localize RhoE, antagonizing ROCK-driven contractility.

Conclusions:

• Discoidin domain receptor 1 (DDR1) is a critical regulator of collective cancer cell invasion.
• The DDR1-Par3/Par6-RhoE pathway controls actomyosin contractility at cell junctions, maintaining cell cohesion.
• Targeting this pathway could offer new strategies to inhibit cancer cell invasion.