Wnt signaling is modulated by the buffer-like properties of cadherins.
1/5 보강
β-catenin is a critical effector of the Wnt pathway and a key component of the cadherin complex.
APA
Schnitkey L, Anthony C, et al. (2026). Wnt signaling is modulated by the buffer-like properties of cadherins.. Molecular biology of the cell, 37(3), ar19. https://doi.org/10.1091/mbc.E25-04-0191
MLA
Schnitkey L, et al.. "Wnt signaling is modulated by the buffer-like properties of cadherins.." Molecular biology of the cell, vol. 37, no. 3, 2026, pp. ar19.
PMID
41537764 ↗
Abstract 한글 요약
β-catenin is a critical effector of the Wnt pathway and a key component of the cadherin complex. Whether Wnt-regulated cytoplasmic β-catenin interacts with the cadherin-associated pool under physiological conditions is unclear. Using a cell line depleted of N- and E-cadherins, we demonstrate that cadherin-depleted cells exhibit lower levels of basal b-catenin that plateau to a similar level as the parental line with Wnt3a stimulation. The cadherin-depleted line exhibits significantly enhanced levels of Wnt signaling by comparison to its parental control; these effects are reversed by wild-type E-cadherin but not E-cadherin with disrupted b-catenin-binding. Enhanced Wnt signaling in the cadherin-depleted line is consistent with a previous study showing that Wnt pathway activation correlates with fold changes in β-catenin levels, rather than the absolute concentration. Our mathematical modeling suggests a mechanism in which β-catenin binding to cadherins acts as a sink to maintain elevated cytoplasmic b-catenin levels in the face of b-catenin destruction complex activity, and also limits pathway response. Our bioinformatic analysis reveals a correlation between elevated Wnt target gene expression and E-cadherin loss in a Wnt-driven model of thyroid cancer. Our results have relevance for tumorigenesis, as cadherin loss is commonly associated with poor prognosis and increased metastatic potential.
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