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Updated: Apr 27, 2026
Modeling Paracrine Noncanonical Wnt Signaling In Vitro
Published on: December 10, 2021
Aldolase positively regulates of the canonical Wnt signaling pathway
Michal Caspi, Gili Perry, Nir Skalka
1Department of Clinical Microbiology and Immunology, Sackler Faculty School of Medicine, Tel Aviv University, Ramat-Aviv, Tel Aviv 69978, Israel. arina@post.tau.ac.il.
Abstract:
The Wnt signaling pathway is an evolutionary conserved system, having pivotal roles during animal development. When over-activated, this signaling pathway is involved in cancer initiation and progression. The canonical Wnt pathway regulates the stability of β-catenin primarily by a destruction complex containing a number of different proteins, including Glycogen synthase kinase 3β (GSK-3β) and Axin, that promote proteasomal degradation of β-catenin. As this signaling cascade is modified by various proteins, novel screens aimed at identifying new Wnt signaling regulators were conducted in our laboratory. One of the different genes that were identified as Wnt signaling activators was Aldolase C (ALDOC). Here we report that ALDOC, Aldolase A (ALDOA) and Aldolase B (ALDOB) activate Wnt signaling in a GSK-3β-dependent mechanism, by disrupting the GSK-3β-Axin interaction and targeting Axin to the dishevelled (Dvl)-induced signalosomes that positively regulate the Wnt pathway thus placing the Aldolase proteins as novel Wnt signaling regulators.
Insights
Aldolase proteins (ALDOC, ALDOA, ALDOB) are identified as novel regulators of the Wnt signaling pathway. They activate this pathway by disrupting the GSK-3β-Axin interaction, impacting cancer development.
Area of Science:
- Molecular Biology
- Cell Signaling
- Biochemistry
Background:
- The Wnt signaling pathway is crucial for animal development and its dysregulation is linked to cancer initiation and progression.
- Canonical Wnt signaling involves a destruction complex targeting β-catenin for degradation, regulated by proteins like Glycogen synthase kinase 3β (GSK-3β) and Axin.
Purpose of the Study:
- To identify novel regulators of the Wnt signaling pathway.
- To investigate the role of Aldolase C (ALDOC) and related proteins in Wnt signaling.
Main Methods:
- Novel genetic screens were employed to identify Wnt signaling activators.
- Experimental validation of identified genes, including Aldolase C (ALDOC), Aldolase A (ALDOA), and Aldolase B (ALDOB).
Main Results:
- ALDOC, ALDOA, and ALDOB were identified as Wnt signaling activators.
- These aldolase proteins activate Wnt signaling through a GSK-3β-dependent mechanism.
- Aldolases disrupt the GSK-3β-Axin interaction and target Axin to Dvl-induced signalosomes.
Conclusions:
- Aldolase proteins (ALDOC, ALDOA, ALDOB) are novel regulators of the Wnt signaling pathway.
- Their mechanism involves modulating the GSK-3β-Axin interaction and influencing Axin localization.
- These findings provide new insights into Wnt pathway regulation and its implications in cancer.
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