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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...
Autores principales: | , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2010
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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 |
Sumario: | 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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