The Wnt Pathway: From Signaling Mechanisms to Synthetic Modulators

Ellen Youngsoo Rim, Hans Clevers, Roel Nusse

Research output: Contribution to journal/periodicalBook/Film/Article reviewScientific

67 Citations (Scopus)


The Wnt pathway is central to a host of developmental and disease-related processes. The remarkable conservation of this intercellular signaling cascade throughout metazoan lineages indicates that it coevolved with multicellularity to regulate the generation and spatial arrangement of distinct cell types. By regulating cell fate specification, mitotic activity, and cell polarity, Wnt signaling orchestrates development and tissue homeostasis, and its dysregulation is implicated in developmental defects, cancer, and degenerative disorders. We review advances in our understanding of this key pathway, from Wnt protein production and secretion to relay of the signal in the cytoplasm of the receiving cell. We discuss the evolutionary history of this pathway as well as endogenous and synthetic modulators of its activity. Finally, we highlight remaining gaps in our knowledge of Wnt signal transduction and avenues for future research.

Original languageEnglish
Pages (from-to)571-598
Number of pages28
JournalAnnual Review of Biochemistry
Publication statusPublished - 21 Jun 2022


  • Animals
  • Cell Differentiation
  • Neoplasms/genetics
  • Wnt Proteins/genetics
  • Wnt Signaling Pathway/physiology
  • beta Catenin/metabolism


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