It was been well established that the Activin A signaling pathway plays a pivotal role in the developing, adult, and diseased organism, commonly acting as a growth inhibitor. Though prevalent in embryonic tissues, Activin A secretion is downregulated in post-natal tissues. Contrary to its function, Activin A expression is often upregulated in cancer, and, of particular interest, in esophageal (ESCC) and head and neck squamous (HNSCC) cell carcinomas. Therefore, we investigated the function of Activin A in these contexts. Interestingly, we found that Activin A acts as an inhibitor of invasion and regulator of the extracellular matrix on dysplastic and ESCC cell lines that retain expression of Activin A receptor type IB, ACVRIB. When ACVRIB is lost, Activin A no longer exerts these effects, though the other components of the Activin A receptor complex remained intact. Consequently, we decided to further define the functional effects of loss of ACVRIB in HNSCC and ESCC cells using CRISPR/Cas9 and siRNA, respectively. In the absence of ACVRIB, we found increased proliferation, migration, and invasion. Using an organoptypic culture system and immunofluorescence staining, we observed altered expression of proteins responsible for cell-cell and cell-extracellular matrix adhesion. We conclude that ACVRIB-dependent Activin A signaling is necessary to regulate ESCC and HNSCC progression.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-04282017-095747 |
| Date | 11 May 2017 |
| Creators | Loomans, Holli Ann |
| Contributors | J. Ann Richmond, Hal Moses, Alissa Weaver, Andries Zijlstra |
| 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-04282017-095747/ |
| Rights | restrictsix, 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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