ARHGAP18: an endogenous inhibitor of angiogenesis, limiting tip formation and stabilizing junctions.
Garry HK Chang, Angelina J Lay, Ka Ka Ting, Yang Zhao, Paul R Coleman, Elizabeth E Powter, Ann Formaz-Preston, Christopher J Jolly, Neil I Bower, Benjamin M Hogan, Silke Rinkwitz, Thomas S Becker, Mathew A Vadas, Jennifer R Gamble
Small GTPases | Published : 2014
The formation of the vascular network requires a tightly controlled balance of pro-angiogenic and stabilizing signals. Perturbation of this balance can result in dysregulated blood vessel morphogenesis and drive pathologies including cancer. Here, we have identified a novel gene, ARHGAP18, as an endogenous negative regulator of angiogenesis, limiting pro-angiogenic signaling and promoting vascular stability. Loss of ARHGAP18 promotes EC hypersprouting during zebrafish and murine retinal vessel development and enhances tumor vascularization and growth. Endogenous ARHGAP18 acts specifically on RhoC and relocalizes to the angiogenic and destabilized EC junctions in a ROCK dependent manner, wher..View full abstract