Enhanced RhoA signalling stabilizes E-cadherin in migrating epithelial monolayers

Area of Science:

• Cell biology
• Biophysics
• Developmental biology

Background:

• Epithelial tissues migrate collectively, accumulating mechanical stress during movement.
• Previous research suggested tensile stress arises from cells pulling on adhesions.
• The specific molecular mechanisms driving this tension were not fully understood.

Purpose of the Study:

• To investigate the role of RhoA-mediated contractility in epithelial tension during collective cell migration.
• To identify upstream regulators of RhoA activity at adherens junctions.
• To determine the functional significance of junctional contractility for epithelial integrity and movement.

Main Methods:

• Utilized MCF-7 cell monolayers for studying epithelial migration.
• Measured active RhoA levels at cell-cell junctions using specific assays.
• Assessed actomyosin levels and mechanical tension in migrating epithelia.
• Manipulated anillin to restore RhoA activity specifically at adherens junctions.

Main Results:

• Active RhoA levels were stimulated by p114 RhoGEF (ARHGEF18) at junctions of migrating MCF-7 cells.
• Increased RhoA activity correlated with elevated actomyosin and mechanical tension.
• Restoring junctional RhoA stabilized E-cadherin (CDH1) at adherens junctions.
• This stabilization promoted orderly collective epithelial movement.

Conclusions:

• Epithelial tension during migration is significantly influenced by RhoA-mediated contractility at adherens junctions.
• p114 RhoGEF acts as a key regulator of junctional RhoA activity.
• RhoA-mediated stabilization of E-cadherin is crucial for maintaining cell-cell adhesion and facilitating organized collective cell migration.