ARHGAP18: an endogenous inhibitor of angiogenesis, limiting tip formation and stabilizing junctions

Chang, Garry H. K., Lay, Angelina J., Ting, Ka Ka, Zhao, Yang, Coleman, Paul R., Powter, Elizabeth E., Formaz-Preston, Ann, Jolly,Christopher J., Bower, Neil I., Hogan, Benjamin M., Rinkwitz, Silke, Becker, Thomas S., Vardas, Mathew A. and Gamble, Jennifer R. (2014) ARHGAP18: an endogenous inhibitor of angiogenesis, limiting tip formation and stabilizing junctions. Small GTPases, 5 3: . doi:10.4161/21541248.2014.975002


Author Chang, Garry H. K.
Lay, Angelina J.
Ting, Ka Ka
Zhao, Yang
Coleman, Paul R.
Powter, Elizabeth E.
Formaz-Preston, Ann
Jolly,Christopher J.
Bower, Neil I.
Hogan, Benjamin M.
Rinkwitz, Silke
Becker, Thomas S.
Vardas, Mathew A.
Gamble, Jennifer R.
Title ARHGAP18: an endogenous inhibitor of angiogenesis, limiting tip formation and stabilizing junctions
Journal name Small GTPases   Check publisher's open access policy
ISSN 2154-1248
2154-1248
Publication date 2014-12-13
Year available 2014
Sub-type Article (original research)
DOI 10.4161/21541248.2014.975002
Open Access Status
Volume 5
Issue 3
Total pages 15
Place of publication London, United Kingdom
Publisher Taylor and Fancis
Collection year 2015
Language eng
Formatted abstract
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, where it is important in reaffirming stable EC junctions and suppressing tip cell behavior, at least
partially through regulation of tip cell genes, Dll4, Flk-1 and Flt-4. These findings highlight ARHGAP18 as a specific
RhoGAP to fine tune vascular morphogenesis, limiting tip cell formation and promoting junctional integrity to stabilize
the angiogenic architecture.
Keyword Angiogenesis
Cell junctions
Sprouting
Arhgap18
Senex
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Fri, 16 Jan 2015, 09:06:00 EST by Susan Allen on behalf of Institute for Molecular Bioscience