Show simple item record

dc.contributor.authorParker, Taybor W.
dc.contributor.authorRudeen, Aaron J.
dc.contributor.authorNeufeld, Kristi L.
dc.identifier.citationParker, T. W., Rudeen, A. J., & Neufeld, K. L. (2020). Oncogenic Serine 45-Deleted β-Catenin Remains Susceptible to Wnt Stimulation and APC Regulation in Human Colonocytes. Cancers, 12(8), 2114.
dc.descriptionThis work is licensed under a Creative Commons Attribution 4.0 International License.en_US
dc.description.abstractThe 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.description.sponsorshipNational Science Foundation (IOS-1456538)en_US
dc.description.sponsorshipNIH P30CA168524en_US
dc.rights© 2020 by the authors. Licensee MDPI, Basel, Switzerland.en_US
dc.subjectWnt signalingen_US
dc.subjectJust-right signalingen_US
dc.subjectColorectal canceren_US
dc.titleOncogenic Serine 45-Deleted β-Catenin Remains Susceptible to Wnt Stimulation and APC Regulation in Human Colonocytesen_US
kusw.kuauthorParker, Taybor W.
kusw.kuauthorRudeen, Aaron J.
kusw.kuauthorNeufeld, Kristi L.
kusw.kudepartmentMolecular Biosciencesen_US
kusw.oanotesPer Sherpa Romeo 11/10/2020:

Cancers [Open panel below]Publication Information TitleCancers [English] ISSNsElectronic: 2072-6694 URL PublishersMDPI [Commercial Publisher] DOAJ Listing Requires APCYes [Data provided by DOAJ] [Open panel below]Publisher Policy Open Access pathways permitted by this journal's policy are listed below by article version. Click on a pathway for a more detailed view.

Published Version NoneCC BYPMC Any Repository, Journal Website, +1 OA PublishingThis pathway includes Open Access publishing EmbargoNo Embargo LicenceCC BY 4.0 Copyright OwnerAuthors Publisher DepositPubMed Central Location Any Repository Named Repository (PubMed Central) Journal Website ConditionsPublished source must be acknowledged with citation NotesAuthors are encouraged to submit their published articles to institutional repositories
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US

Files in this item


This item appears in the following Collection(s)

Show simple item record

© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Except where otherwise noted, this item's license is described as: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.