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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.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US

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© 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.