Angiomotin Is A Novel Cadherin-11 Interacting Protein That Mediates Migration In Prostate Cancer Cells

<p>Prostate cancer (PCa), the second leading cause of cancer-related deaths among men in the United States, has the proclivity to metastasize to bone resulting in sclerotic lesions. These cancer induced bone growths cause bone pain and fractures. Therefore, understanding the molecular mechanisms contributing to PCa bone metastasis is required in order to find better prognostic tools and suitable targets for metastasis treatment and/ or prevention. Previous work in our laboratory showed increased expression of cadherin-11 (Cad11), a mesenchymal cadherin, during PCa progression. Furthermore, Cad11 expression endows PCa cells with increased migratory potential and metastasis to bone. Deletion of the Cad11 cytoplasmic region (cyto) resulted in loss of cell migration. How the Cad11 cytoplasmic domain mediates cell migration is unknown. We have identified angiomotin (Amot), a regulator of endothelial cell migration and epithelial cell polarity, as a Cad11 interacting protein. Deletion analysis showed that the last C-terminal 10 amino acids in Cad11 mediated Amot binding. Further, Cad11 preferentially interacts with the Amot-p80 isoform than the Amot-p130. Analysis of Amot mutants showed that Amot-p80 interacts with Cad11 through its middle domain, not the well characterized coiled-coil domains or PDZ motif. Deletion of the last ten Cad11 residues significantly reduced Cad11-mediated cell migration in C4-2B4, PC3-mm2, and HEK293T cells, compared to cells expressing wild-type Cad11. Together, our studies identified and characterized Amot-p80 as a novel Cad11 binding protein that promotes Cad11-mediated PCa cell migration.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2014

Author dc:creator

• Ortiz, Angelica

Contributors dc:contributor

• Sue-Hwa Lin
• Gary Gallick
• Pierre McCrea

• Cadherin-11
• Angiomotin
• Prostate Cancer
• Cell Migration
• Biochemistry
• Cancer Biology

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/505

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1545