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 IKKÑ both induce endothelial EMT and endothelial cell motility. This can be blocked with co-expression of IÛB-Ñ, suggesting that endothelial EMT is mediated through the NF-ÛB canonical pathway. Vav1 and Ô-catenin are both upregulated by IKKÑ. Vav1 is required for induction of endothelial EMT, and induces endothelial motility and tumor angiogenesis. Ô-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/IKKÑ/Vav1 signaling pathway can induce endothelial EMT and that this process plays a role in tumor angiogenesis.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-03312008-163540 |
| Date | 28 April 2008 |
| Creators | DeBusk, Laura M |
| Contributors | Charles Lin, Dennis Hallahan, Jin Chen, Ann Richmond, Scott Baldwin |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-03312008-163540/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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