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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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Detalles Bibliográficos
Autores principales: Harris, Elizabeth S., Nelson, W. James
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
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.
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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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