Canonical Wnt signaling is a pivotal regulatory pathway orchestrating cell fate determination, proliferation, and tissue homeostasis in both embryonic development and adulthood. Dysregulation of canonical Wnt signaling is implicated in diverse pathological conditions, including cancer, fibrosis, and degenerative diseases. In recent years, our understanding of canonical Wnt regulation has expanded beyond core components to embrace a complex landscape of intracellular signaling crosstalk.

One example is the dynamic interplay between the Hippo pathway effectors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) and canonical Wnt effectors such as β-catenin. Emerging evidence demonstrates that YAP and TAZ can both antagonize and synergize with Wnt/β-catenin signaling in a context-dependent manner, influencing gene expression programs central to organogenesis, regeneration, and tumorigenesis.

This Research Topic aims to gather the latest research, comprehensive reviews, methodological advances, and expert perspectives on the mechanisms and outcomes of crosstalk between canonical Wnts and other signaling pathways linked to, for example, Hedgehog, NF-κB, hypoxia-inducible factor-1α, Notch, or even the non-canonical Wnts. Understanding this integration holds potential for unravelling fundamental biological processes, clarifying unresolved questions in stem cell and cancer biology, and paving the way for new therapeutic strategies. We seek contributions that provide novel insights, critically examine current models, present innovative technologies, or offer fresh viewpoints on the challenges and opportunities in this rapidly evolving field.

We invite submissions in these areas:

o Mechanistic studies of Wnt-crosstalk, including direct interactions and context-dependent regulatory outcomes

o Physiological and pathological implications in development, regeneration, cancer, and disease progression

o Technological advances for studying and dissecting signaling interplay

o Therapeutic opportunities and challenges in targeting this crosstalk

o Intersection of Wnt pathway crosstalk with other major signaling pathways and networks

o Reviews, opinions, and perspectives highlighting current controversies, emerging approaches, and future research directions

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Crosstalk on Canonical Wnt Signaling