ArticleProceedings of the National Academy of Sciences of the United States of America2023
Feedback in the β-catenin destruction complex imparts bistability and cellular memory.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Tumor-Intrinsic HEXB Drives Endothelial-To-Mesenchymal Transition and Confers Resistance to Anti-Angiogenic Therapy in Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Convergent mechanisms in Wnt and Hedgehog signaling.Science signaling · 2026Review
- Ras-MAPK inhibition induces AXIN1 loss in colorectal cancer by mTOR associated suppression of protein synthesis.Cell communication and signaling : CCS · 2026Article
- Preservation of Human Colonic Stem Cells Requires an ERK Dynamics Checkpoint Mediated by AKT.bioRxiv : the preprint server for biology · 2026Article
- Wnt signaling is modulated by the buffer-like properties of cadherins.Molecular biology of the cell · 2026Article
- GSK-3 and BCL-XL inhibition mitigates the competitive advantage of APC-mutant colorectal cancer cells.Oncogenesis · 2025Article
- A Putative Frizzled 7-Targeting Compound Acts as a Firefly Luciferase Inhibitor.Journal of medicinal chemistry · 2024Article
- Wnt/β-catenin signaling in the development and therapeutic resistance of non-small cell lung cancer.Journal of translational medicine · 2024Review
- The mechanisms of class 1A PI3K and Wnt/β-catenin coupled signaling in breast cancer.Biochemical Society transactions · 2023Review
- Article
- Podocytes derived from human induced pluripotent stem cells: characterization, comparison, and modeling of diabetic kidney disease.Stem cell research & therapy · 2022Article
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Authors and funding
13 authors.
Funding
Abstract
Wnt ligands are considered classical morphogens, for which the strength of the cellular response is proportional to the concentration of the ligand. Herein, we show an emergent property of bistability arising from feedback among the Wnt destruction complex proteins that target the key transcriptional co-activator β-catenin for degradation. Using biochemical reconstitution, we identified positive feedback between the scaffold protein Axin and the kinase glycogen synthase kinase 3 (GSK3). Theoretical modeling of this feedback between Axin and GSK3 suggested that the activity of the destruction complex exhibits bistable behavior. We experimentally confirmed these predictions by demonstrating that cellular cytoplasmic β-catenin concentrations exhibit an "all-or-none" response with sustained memory (hysteresis) of the signaling input. This bistable behavior was transformed into a graded response and memory was lost through inhibition of GSK3. These findings provide a mechanism for establishing decisive, switch-like cellular response and memory upon Wnt pathway stimulation.
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