Can We Pharmacologically Target Dishevelled: The Key Signal Transducer in the Wnt Pathways?

Area of Science:

• Molecular Biology
• Cell Signaling
• Oncology

Background:

• Dishevelled (DVL) acts as a central signal transducer in Wnt/β-catenin-dependent and independent pathways.
• DVL is crucial for linking receptor complexes to downstream effectors.
• Aberrant Wnt signaling, often involving DVL upregulation, is implicated in various cancers.

Purpose of the Study:

• To review current strategies for modulating Dishevelled (DVL) function.
• To highlight DVL as a therapeutic target for Wnt-addicted cancers and related disorders.
• To discuss novel research directions for Wnt signaling inhibition via DVL.

Main Methods:

• Modulation of enzymes controlling DVL post-translational modifications (e.g., kinase inhibition, ubiquitination promotion).
• Targeting protein-protein interactions involving DVL domains (DIX, DEP, PDZ).
• Inhibition of DVL polymerization and ligand interactions.

Main Results:

• Several approaches show promise for inhibiting Wnt signaling by targeting DVL.
• Post-translational modification of DVL offers a viable therapeutic avenue.
• Directly interfering with DVL's functional domains presents new therapeutic possibilities.

Conclusions:

• Targeting Dishevelled (DVL) is a promising strategy for treating cancers driven by aberrant Wnt signaling.
• Further research into DVL modulation, including post-translational modifications and domain interactions, is warranted.
• Inhibiting DVL function offers a potential therapeutic window for Wnt-related diseases.