VE-cadherin junction dynamics in initial lymphatic vessels promotes lymph node metastasis.

ABSTRACT: The endothelial junction component vascular endothelial (VE)-cadherin governs junctional dynamics in the blood and lymphatic vasculature. Here, we explored how lymphatic junction stability is modulated by elevated VEGFA signaling to facilitate metastasis to sentinel lymph nodes. Zippering of VE-cadherin junctions was established in dermal initial lymphatic vessels after VEGFA injection and in tumor-proximal lymphatics in mice. Shape analysis of pan-cellular VE-cadherin fragments revealed that junctional zippering was accompanied by accumulation of small round-shaped VE-cadherin fragments in the lymphatic endothelium. In mice expressing a mutant VEGFR2 lacking the Y949 phosphosite (Vegfr2 ^Y949F/Y949F ) required for activation of Src family kinases, zippering of lymp

SUBMITTER: Sainz-Jaspeado M 

PROVIDER: S-EPMC10751244 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature