Toronto team finds CSNK1 proximity degrades β-catenin in colorectal cancer cells in vitro
A genome-scale screen at the University of Toronto found that bringing Casein kinase I close to β-catenin triggers its degradation and slows growth of colorectal cancer cells with Wnt mutations.
Researchers at the Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, reported a genome-scale screen for proteins whose induced proximity to β-catenin reduces its levels in colorectal cancer cells. The work, led by Lucie Wolf, Mikko Taipale and Stéphane Angers, was published on 7 November 2026 in Nature Communications nature.com
Nature Communicationsnature.comOpen source ↗. The experiments were carried out in cultured cells.
Wnt pathway and induced proximity
β-catenin is the central effector of Wnt signaling. According to the authors, therapeutic strategies that inhibit this pathway in cancer have so far failed to advance to the clinic. Induced-proximity drugs, which bring a target close to a protein that alters its fate, are described as expanding the range of targets previously considered undruggable.
The team used an unbiased genome-scale approach to look for candidate proteins that, when brought near β-catenin, inhibit it in colorectal cancer cells. Several E3 ubiquitin ligases were among the hits, which the authors consider a validation of the approach.
Casein kinase I and β-catenin degradation
The screen also showed that inducing proximity to members of the Casein kinase I (CSNK1) family leads to β-catenin degradation nature.com
Nature Communicationsnature.comOpen source ↗. This inhibited the growth of colorectal cancer cells that carry Wnt pathway mutations.
The authors report that degradation induced by CSNK1 proximity depends on kinase activity and on the proteasome. In other words, the enzymatic function of the recruited kinase and the cell's proteasomal machinery are both required for the effect.
The authors propose that recruiting a kinase can form a neo-degron, a new degradation signal on the target, and that this can broaden the targeting strategies available to induced-proximity drugs. The material does not describe tests in animals or in patients; the results relate to cell-based experiments.
The study is open access under a CC BY-NC-ND 4.0 licence. Funding came from the Deutsche Forschungsgemeinschaft, the Charles H. Best Postdoctoral Fellowship and the Canadian Institutes of Health Research.
