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Adenomatous Polyposis Coli Regulates Endothelial Cell Migration Independent of Roles in β-Catenin Signaling and Cell–Cell Adhesion
Adenomatous polyposis coli (APC), a tumor suppressor commonly mutated in cancer, is a cytoskeletal organizer for cell migration and a scaffold for GSK3β/CKI-mediated phosphorylation and degradation of the Wnt effector β-catenin. It remains unclear whether these different APC functions are coupled, o...
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Formato: | Texto |
Lenguaje: | English |
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The American Society for Cell Biology
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912348/ https://www.ncbi.nlm.nih.gov/pubmed/20519433 http://dx.doi.org/10.1091/mbc.E10-03-0235 |
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author | Harris, Elizabeth S. Nelson, W. James |
author_facet | Harris, Elizabeth S. Nelson, W. James |
author_sort | Harris, Elizabeth S. |
collection | PubMed |
description | Adenomatous polyposis coli (APC), a tumor suppressor commonly mutated in cancer, is a cytoskeletal organizer for cell migration and a scaffold for GSK3β/CKI-mediated phosphorylation and degradation of the Wnt effector β-catenin. It remains unclear whether these different APC functions are coupled, or independently regulated and localized. In primary endothelial cells, we show that GSK3β/CKI-phosphorylated APC localizes to microtubule-dependent clusters at the tips of membrane extensions. Loss of GSK3β/CKI-phosphorylated APC from these clusters correlates with a decrease in cell migration. GSK3β/CKI-phosphorylated APC and β-catenin at clusters is degraded rapidly by the proteasome, but inhibition of GSK3β/CKI does not increase β-catenin–mediated transcription. GSK3β/CKI-phosphorylated and -nonphosphorylated APC also localize along adherens junctions, which requires actin and cell–cell adhesion. Significantly, inhibition of cell–cell adhesion results in loss of lateral membrane APC and a concomitant increase in GSK3β/CKI-phosphorylated APC in clusters. These results uncouple different APC functions and show that GSK3β/CKI phosphorylation regulates APC clusters and cell migration independently of cell–cell adhesion and β-catenin transcriptional activity. |
format | Text |
id | pubmed-2912348 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-29123482010-10-16 Adenomatous Polyposis Coli Regulates Endothelial Cell Migration Independent of Roles in β-Catenin Signaling and Cell–Cell Adhesion Harris, Elizabeth S. Nelson, W. James Mol Biol Cell Articles Adenomatous polyposis coli (APC), a tumor suppressor commonly mutated in cancer, is a cytoskeletal organizer for cell migration and a scaffold for GSK3β/CKI-mediated phosphorylation and degradation of the Wnt effector β-catenin. It remains unclear whether these different APC functions are coupled, or independently regulated and localized. In primary endothelial cells, we show that GSK3β/CKI-phosphorylated APC localizes to microtubule-dependent clusters at the tips of membrane extensions. Loss of GSK3β/CKI-phosphorylated APC from these clusters correlates with a decrease in cell migration. GSK3β/CKI-phosphorylated APC and β-catenin at clusters is degraded rapidly by the proteasome, but inhibition of GSK3β/CKI does not increase β-catenin–mediated transcription. GSK3β/CKI-phosphorylated and -nonphosphorylated APC also localize along adherens junctions, which requires actin and cell–cell adhesion. Significantly, inhibition of cell–cell adhesion results in loss of lateral membrane APC and a concomitant increase in GSK3β/CKI-phosphorylated APC in clusters. These results uncouple different APC functions and show that GSK3β/CKI phosphorylation regulates APC clusters and cell migration independently of cell–cell adhesion and β-catenin transcriptional activity. The American Society for Cell Biology 2010-08-01 /pmc/articles/PMC2912348/ /pubmed/20519433 http://dx.doi.org/10.1091/mbc.E10-03-0235 Text en © 2010 by The American Society for Cell Biology |
spellingShingle | Articles Harris, Elizabeth S. Nelson, W. James Adenomatous Polyposis Coli Regulates Endothelial Cell Migration Independent of Roles in β-Catenin Signaling and Cell–Cell Adhesion |
title | Adenomatous Polyposis Coli Regulates Endothelial Cell Migration Independent of Roles in β-Catenin Signaling and Cell–Cell Adhesion |
title_full | Adenomatous Polyposis Coli Regulates Endothelial Cell Migration Independent of Roles in β-Catenin Signaling and Cell–Cell Adhesion |
title_fullStr | Adenomatous Polyposis Coli Regulates Endothelial Cell Migration Independent of Roles in β-Catenin Signaling and Cell–Cell Adhesion |
title_full_unstemmed | Adenomatous Polyposis Coli Regulates Endothelial Cell Migration Independent of Roles in β-Catenin Signaling and Cell–Cell Adhesion |
title_short | Adenomatous Polyposis Coli Regulates Endothelial Cell Migration Independent of Roles in β-Catenin Signaling and Cell–Cell Adhesion |
title_sort | adenomatous polyposis coli regulates endothelial cell migration independent of roles in β-catenin signaling and cell–cell adhesion |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912348/ https://www.ncbi.nlm.nih.gov/pubmed/20519433 http://dx.doi.org/10.1091/mbc.E10-03-0235 |
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