Cadherins

Loss of VEGF-C or VEGFR3 function or gain of VE-cadherin function causes identical defects in sinusoidal and lymphatic growth, resulting in anemia and lymphedema. Mechanistically, VEGF-C drives VE-cadherin phosphorylation and endocytosis whereas VE-cadherin prevents VEGFR3 internalization and downstream growth factor signaling. In the absence of VEGFR3, reducing VE-cadherin levels rescues vascular growth by potentiating VEGF-C–VEGFR2 signaling.

Epithelial cells form energetically costly cell–cell adhesions in response to mechanical forces. How cells obtain their energy during this event is unclear. Activity of a key regulator of cell metabolism, the AMP-activated protein kinase (AMPK), is now shown to be mechanoresponsive, and thus can bridge adhesion mechanotransduction and energy homeostasis.

Tumours are highly complex and contain multiple cell types. Cancer-associated fibroblasts are now shown to have a critical role in directly leading cancer cell invasion. This intercellular interaction relies on a mechanically active cadherin-based junction, and CAF-led invasion is demonstrated to require E-cadherin in the cancer cell.

Cadherin adhesion complexes have recently emerged as sensors of tissue tension that regulate key developmental processes. Super-resolution microscopy experiments now unravel the spatial organization of the interface between cadherins and the actin cytoskeleton and reveal how vinculin, a central component in cadherin mechanotransduction, is regulated by mechanical and biochemical signals.

Many cell types in our body move in a collective manner, which requires individual cells to align their movements relative to that of their neighbours. A mechanism is now described in which cadherin-rich protrusions are extended from leading migrating cells and engulfed by follower cells to guide collective migration.