Modification of VE-cadherin signalling by ZEB1 in Lymphatic Endothelial Cells

Recent studies suggest that endothelial ZEB1 signalling promotes blood vessel growth and reduces junctional integrity, although the underlying mechanisms remain unclear. Notably, the role of ZEB1 in the lymphatic vasculature is unknown, and the regulation of lymphatic integrity by VE-cadherin remains poorly defined.

Here, using an integrated proteomic and transcriptomic approach, we identify ZEB1-dependent signalling pathways associated with cell–cell junction reorganisation in lymphatic endothelial cells (LECs). Loss of ZEB1 reduced VE-cadherin phosphorylation at pY731 and pY685 and was accompanied by decreased monolayer resistance and impedance, together with increased leukocyte transendothelial migration. ZEB1 knockdown also reduced YES tyrosine kinase expression and altered YAP1 expression and junctional localisation, changes that were associated with reduced VE-cadherin phosphorylation.