| Type of Document |
Dissertation |
| Author |
DeBusk, Laura M
|
| Author's Email Address |
laura.debusk@vanderbilt.edu |
| URN |
etd-03312008-163540 |
| Title |
AKT/IKKα/VAV1 signaling in endothelial cell survival and angiogenesis |
| Degree |
PhD |
| Department |
Cancer Biology |
| Advisory Committee |
| Advisor Name |
Title |
| Dennis Hallahan |
Committee Chair |
| Ann Richmond |
Committee Member |
| Charles Lin |
Committee Member |
| Jin Chen |
Committee Member |
| Scott Baldwin |
Committee Member |
|
| Keywords |
- angiogenesis
- Neovascularization -- Regulation
- Vascular endothelial growth factors -- Pathophysiology
- Cellular control mechanisms
|
| Date of Defense |
2008-03-25 |
| Availability |
unrestricted |
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.
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| Files |
| Filename |
Size |
Approximate Download Time
(Hours:Minutes:Seconds)
|
| 28.8 Modem |
56K Modem |
ISDN (64 Kb) |
ISDN (128 Kb) |
Higher-speed Access |
| |
DeBusk.pdf |
3.18 Mb |
00:14:43 |
00:07:34 |
00:06:37 |
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