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Updated: Jun 16, 2025

Modeling Paracrine Noncanonical Wnt Signaling In Vitro
Published on: December 10, 2021
Positive cooperativity in synergistic activation of Wnt proteins
Clemence Bonnet1,2, Christiana S Han1, Sophie X Deng1,3
1Stein Eye Institute, University of California, Los Angeles, CA, 90095, USA.
Background:
Wnt proteins are crucial for embryonic development, stem cell growth, and tissue regeneration. Wnt signaling pathway is activated when Wnt proteins bind to cell membrane receptors.
Methods And Results:
We employed a luciferase reporter assay in HEK293STF cells to measure Wnt protein-induced signaling. We observed that Wnt3a uniquely promotes the Wnt/β-catenin pathway through positive cooperativity. Additionally, MFH-ND, a molecular mimic of Wnt ligands, markedly increased Wnt3a-induced signaling in a dose-responsive manner. This suggests that various Wnt ligands can synergistically enhance Wnt pathway activation.
Conclusions:
The study suggests the likelihood of various Wnt ligands coexisting in a single signalosome on the cell membrane, providing new insights into the complexities of Wnt signaling mechanisms.
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