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Wnt signalling and its impact on development and cancer

Abstract

The Wnt signalling pathway is an ancient system that has been highly conserved during evolution. It has a crucial role in the embryonic development of all animal species, in the regeneration of tissues in adult organisms and in many other processes. Mutations or deregulated expression of components of the Wnt pathway can induce disease, most importantly cancer. The first gene to be identified that encodes a Wnt signalling component, Int1 (integration 1), was molecularly characterized from mouse tumour cells 25 years ago. In parallel, the homologous gene Wingless in Drosophila melanogaster, which produces developmental defects in embryos, was characterized. Since then, further components of the Wnt pathway have been identified and their epistatic relationships have been defined. This article is a Timeline of crucial discoveries about the components and functions of this essential pathway.

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Figure 1: The canonical Wnt—β-catenin pathway.
Figure 2: Human APC and CTNNB1 mutations are associated with carcinogenesis.
Figure 3: Cancer therapeutics that target components of the canonical Wnt pathway.

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Acknowledgements

We thank C. Birchmeier and R. Hodge for helpful discussions and improving our text. J. Fritzmann advised us on drugs and clinical aspects. The work of our laboratory is funded by the German Research Foundation (DFG), the German Cancer Aid (Deutsche Krebshilfe), and the German Federal Minister of Research and Technology (BMBF).

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Klaus, A., Birchmeier, W. Wnt signalling and its impact on development and cancer. Nat Rev Cancer 8, 387–398 (2008). https://doi.org/10.1038/nrc2389

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