Cargando…
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...
Autores principales: | , |
---|---|
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 |
_version_ | 1783499368775548928 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7031393 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT parkertayborw apccontrolswntinducedbcatenindestructioncomplexrecruitmentinhumancolonocytes AT neufeldkristil apccontrolswntinducedbcatenindestructioncomplexrecruitmentinhumancolonocytes |