dc.creator | DeBusk, Laura M | |
dc.date.accessioned | 2020-08-22T00:18:17Z | |
dc.date.available | 2010-04-28 | |
dc.date.issued | 2008-04-28 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-03312008-163540 | |
dc.identifier.uri | http://hdl.handle.net/1803/11831 | |
dc.description.abstract | We have identified a novel signaling pathway, AKT/IKKα/VAV1, which induces endothelial cell survival and motility. Ang1/Tie2 and VEGF/VEGFR signaling activates Akt and induces cell survival. Akt and IKKƒÑ both induce endothelial EMT and endothelial cell motility. This can be blocked with co-expression of IƒÛB-ƒÑ, suggesting that endothelial EMT is mediated through the NF-ƒÛB canonical pathway. Vav1 and ƒÔ-catenin are both upregulated by IKKƒÑ. Vav1 is required for induction of endothelial EMT, and induces endothelial motility and tumor angiogenesis. ƒÔ-catenin also induces endothelial cell motility and tumor angiogenesis, through regulation of RhoA and Cdc42 activity. The proposed model advances the study of angiogenesis. We demonstrate a novel mechanism for endothelial cell survival and endothelial cell motility. More importantly, we show that the Akt/IKKƒÑ/Vav1 signaling pathway can induce endothelial EMT and that this process plays a role in tumor angiogenesis. | |
dc.format.mimetype | application/pdf | |
dc.subject | angiogenesis | |
dc.subject | Neovascularization -- Regulation | |
dc.subject | Vascular endothelial growth factors -- Pathophysiology | |
dc.subject | Cellular control mechanisms | |
dc.title | AKT/IKKα/VAV1 signaling in endothelial cell survival and angiogenesis | |
dc.type | dissertation | |
dc.contributor.committeeMember | Charles Lin | |
dc.contributor.committeeMember | Jin Chen | |
dc.contributor.committeeMember | Ann Richmond | |
dc.contributor.committeeMember | Scott Baldwin | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Cancer Biology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2010-04-28 | |
local.embargo.lift | 2010-04-28 | |
dc.contributor.committeeChair | Dennis Hallahan | |