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APC controls Wnt-induced β-catenin destruction complex recruitment in human colonocytes

Wnt/β-catenin signaling is essential for intestinal homeostasis and is aberrantly activated in most colorectal cancers (CRC) through mutation of the tumor suppressor Adenomatous Polyposis Coli (APC). APC is an essential component of a cytoplasmic protein complex that targets β-catenin for destructio...

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Autores principales: Parker, Taybor W., Neufeld, Kristi L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031393/
https://www.ncbi.nlm.nih.gov/pubmed/32076059
http://dx.doi.org/10.1038/s41598-020-59899-z
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author Parker, Taybor W.
Neufeld, Kristi L.
author_facet Parker, Taybor W.
Neufeld, Kristi L.
author_sort Parker, Taybor W.
collection PubMed
description Wnt/β-catenin signaling is essential for intestinal homeostasis and is aberrantly activated in most colorectal cancers (CRC) through mutation of the tumor suppressor Adenomatous Polyposis Coli (APC). APC is an essential component of a cytoplasmic protein complex that targets β-catenin for destruction. Following Wnt ligand presentation, this complex is inhibited. However, a role for APC in this inhibition has not been shown. Here, we utilized Wnt3a-beads to locally activate Wnt co-receptors. In response, the endogenous β-catenin destruction complex reoriented toward the local Wnt cue in CRC cells with full-length APC, but not if APC was truncated or depleted. Non-transformed human colon epithelial cells displayed similar Wnt-induced destruction complex localization which appeared to be dependent on APC and less so on Axin. Our results expand the current model of Wnt/β-catenin signaling such that in response to Wnt, the β-catenin destruction complex: (1) maintains composition and binding to β-catenin, (2) moves toward the plasma membrane, and (3) requires full-length APC for this relocalization.
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spelling pubmed-70313932020-02-27 APC controls Wnt-induced β-catenin destruction complex recruitment in human colonocytes Parker, Taybor W. Neufeld, Kristi L. Sci Rep Article Wnt/β-catenin signaling is essential for intestinal homeostasis and is aberrantly activated in most colorectal cancers (CRC) through mutation of the tumor suppressor Adenomatous Polyposis Coli (APC). APC is an essential component of a cytoplasmic protein complex that targets β-catenin for destruction. Following Wnt ligand presentation, this complex is inhibited. However, a role for APC in this inhibition has not been shown. Here, we utilized Wnt3a-beads to locally activate Wnt co-receptors. In response, the endogenous β-catenin destruction complex reoriented toward the local Wnt cue in CRC cells with full-length APC, but not if APC was truncated or depleted. Non-transformed human colon epithelial cells displayed similar Wnt-induced destruction complex localization which appeared to be dependent on APC and less so on Axin. Our results expand the current model of Wnt/β-catenin signaling such that in response to Wnt, the β-catenin destruction complex: (1) maintains composition and binding to β-catenin, (2) moves toward the plasma membrane, and (3) requires full-length APC for this relocalization. Nature Publishing Group UK 2020-02-19 /pmc/articles/PMC7031393/ /pubmed/32076059 http://dx.doi.org/10.1038/s41598-020-59899-z Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Parker, Taybor W.
Neufeld, Kristi L.
APC controls Wnt-induced β-catenin destruction complex recruitment in human colonocytes
title APC controls Wnt-induced β-catenin destruction complex recruitment in human colonocytes
title_full APC controls Wnt-induced β-catenin destruction complex recruitment in human colonocytes
title_fullStr APC controls Wnt-induced β-catenin destruction complex recruitment in human colonocytes
title_full_unstemmed APC controls Wnt-induced β-catenin destruction complex recruitment in human colonocytes
title_short APC controls Wnt-induced β-catenin destruction complex recruitment in human colonocytes
title_sort apc controls wnt-induced β-catenin destruction complex recruitment in human colonocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031393/
https://www.ncbi.nlm.nih.gov/pubmed/32076059
http://dx.doi.org/10.1038/s41598-020-59899-z
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