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Oncogenic Serine 45-Deleted β-Catenin Remains Susceptible to Wnt Stimulation and APC Regulation in Human Colonocytes
dc.contributor.author | Parker, Taybor W. | |
dc.contributor.author | Rudeen, Aaron J. | |
dc.contributor.author | Neufeld, Kristi L. | |
dc.date.accessioned | 2022-09-13T19:10:31Z | |
dc.date.available | 2022-09-13T19:10:31Z | |
dc.date.issued | 2020-07-30 | |
dc.identifier.citation | Parker, T.W.; Rudeen, A.J.; Neufeld, K.L. Oncogenic Serine 45-Deleted β-Catenin Remains Susceptible to Wnt Stimulation and APC Regulation in Human Colonocytes. Cancers 2020, 12, 2114. https://doi.org/10.3390/cancers12082114 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/33468 | |
dc.description.abstract | The Wnt/β-catenin signaling pathway is deregulated in nearly all colorectal cancers (CRCs), predominantly through mutation of the tumor suppressor Adenomatous Polyposis Coli (APC). APC mutation is thought to allow a “just-right” amount of Wnt pathway activation by fine-tuning β-catenin levels. While at a much lower frequency, mutations that result in a β-catenin that is compromised for degradation occur in a subset of human CRCs. Here, we investigate whether one such “stabilized” β-catenin responds to regulatory stimuli, thus allowing β-catenin levels conducive for tumor formation. We utilize cells harboring a single mutant allele encoding Ser45-deleted β-catenin (β-catΔS45) to test the effects of Wnt3a treatment or APC-depletion on β-catΔS45 regulation and activity. We find that APC and β-catΔS45 retain interaction with Wnt receptors. Unexpectedly, β-catΔS45 accumulates and activates TOPflash reporter upon Wnt treatment or APC-depletion, but only accumulates in the nucleus upon APC loss. Finally, we find that β-catenin phosphorylation at GSK-3β sites and proteasomal degradation continue to occur in the absence of Ser45. Our results expand the current understanding of Wnt/β-catenin signaling and provide an example of a β-catenin mutation that maintains some ability to respond to Wnt, a possible key to establishing β-catenin activity that is “just-right” for tumorigenesis. | en_US |
dc.publisher | MDPI | en_US |
dc.rights | © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Wnt signaling | en_US |
dc.subject | Just-right signaling | en_US |
dc.subject | APC | en_US |
dc.subject | β-catenin | en_US |
dc.subject | Colorectal cancer | en_US |
dc.title | Oncogenic Serine 45-Deleted β-Catenin Remains Susceptible to Wnt Stimulation and APC Regulation in Human Colonocytes | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Parker, Taybor W. | |
kusw.kuauthor | Rudeen, Aaron J. | |
kusw.kuauthor | Neufeld, Kristi L. | |
kusw.kudepartment | Molecular Biosciences | en_US |
dc.identifier.doi | 10.3390/cancers12082114 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-3829-7554 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0003-3653-9385 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.rights.accessrights | openAccess | en_US |