Proteins that regulate cell polarity are fundamental for metazoan biology and are necessary for proper development of tissues and organs. In light of polarity genes fundamental role in tissue organization, disruptions in polarity networks have been suspected to promote neoplasia. Studies in Drosophila melanogaster models and correlative data from human tumor samples have supported this hypothesis, but direct experimental support for polarity genes as mammalian tumor suppressors has only recently been reported. The polarity regulator Par3 has emerged as a suppressor of growth and metastasis in mammary and skin tumors. The mechanisms by which Par3 restrains tumor progression, however, remain obscure. In the studies reported here, I show that loss of Par3 can promote activation of an oncogenic signaling pathway in mouse mammary cells by permitting aPKCι/λ to activate NF-κB signaling. These studies demonstrate that preventing aberrant aPKC activity is a key tumor suppressor function of Par3. This mechanism may be relevant to human tumors.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-07172015-083313 |
| Date | 17 July 2015 |
| Creators | Guyer, Richard Allen |
| Contributors | Ethan Lee, Jennifer Pietenpol, Matthew Tyska, Andrea Page-McCaw, Ian Macara |
| 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-07172015-083313/ |
| 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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