dc.creator | Saito-Diaz, Vicente Kenyi | |
dc.date.accessioned | 2020-08-22T00:08:50Z | |
dc.date.available | 2018-03-27 | |
dc.date.issued | 2017-03-27 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-03272017-113107 | |
dc.identifier.uri | http://hdl.handle.net/1803/11541 | |
dc.description.abstract | The Wnt pathway is a highly-conserved pathway that controls many developmental processes and is mutated in many human diseases (e.g., cancer). The tumor suppressor adenomatous polyposis coli (APC) is a critical negative regulator of Wnt signal transduction. Mutations in the APC gene resulting in constitutive activation of the Wnt pathway occur in over 80% of human colorectal cancers (CRC). Despite its critical role in the Wnt pathway, the exact mechanism of APC function in Wnt signal transduction is not clear. The lab developed a monoclonal antibody (mAb7E5) that targets the co-receptor LRP6 and inhibits Wnt signaling in APC-mutant CRC cells. Using the antibody mAb7E5, I found that APC regulates Wnt receptor activation. Furthermore, I found that, in APC-depleted cells, the co-receptor LRP6 is constitutively active in a manner independent of Wnt ligands and that LRP6 is internalized by the clathrin-dependent endocytic machinery. Finally, I demonstrate that APC, clathrin, and the AP-2 adaptor protein interact as a complex. Thus, my studies reveal a new role for APC function in Wnt signal transduction and provide insight into the development of therapeutic agents targeting APC-mutant tumors. | |
dc.format.mimetype | application/pdf | |
dc.subject | endocytosis | |
dc.subject | beta-catenin | |
dc.subject | LRP6 | |
dc.subject | APC | |
dc.subject | Wnt signaling | |
dc.subject | clathrin | |
dc.subject | caveolin | |
dc.subject | colorectal cancer | |
dc.title | Regulation of Wnt Receptor Activation by the Tumor Suppressor APC | |
dc.type | dissertation | |
dc.contributor.committeeMember | Jin Chen | |
dc.contributor.committeeMember | Scott Hiebert | |
dc.contributor.committeeMember | Andrea Page-McCaw | |
dc.contributor.committeeMember | William Tansey | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Cell and Developmental Biology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2018-03-27 | |
local.embargo.lift | 2018-03-27 | |
dc.contributor.committeeChair | Ethan Lee | |