Constitutive Active Mutant TIE2 Induces Enlarged Vascular Lumen Formation with Loss of Apico-basal Polarity and Pericyte Recruitment.

ABSTRACT: Abnormalities in controlling key aspects of angiogenesis including vascular cell migration, lumen formation and vessel maturation are hallmarks of vascular anomalies including venous malformation (VM). Gain-of-function mutations in the tyrosine kinase receptor TIE2 can cause VM and induce a ligand-independent hyperactivation of TIE2. Despite these important findings, the TIE2-dependent mechanisms triggering enlarged vascular lesions are not well understood. Herein we studied TIE2 p.L914F, the most frequent mutation identified in VM patients. We report that endothelial cells harboring a TIE2-L914F mutation display abnormal cell migration due to a loss of front-rear polarity as demonstrated by a non-polarized Golgi apparatus. Utilizing a three-dimensional fibrin-matrix based model we show th

SUBMITTER: Cai Y 

PROVIDER: S-EPMC6710257 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature