Role of the Wnt Signalling Pathway in Cancer


Canonical Wnt/β‐catenin signalling is a highly conserved pathway that plays an essential role during embryonic development. In the adult, the Wnt pathway regulates stem cell maintenance and tissue homeostasis. Inappropriate activation of the Wnt signalling pathway has been implicated in a variety of cancers, most notably in colorectal cancer. Wnt signalling alterations in cancer have been identified at various levels of the pathway: at the membrane, in the cytoplasm and within the nucleus. Given that Wnt signalling plays a critical role in many human cancers, intense investigation has focused on targeting this pathway to develop potential therapeutics for cancer therapy.

Key Concepts

  • Wnt signalling is a highly conserved pathway in development.
  • A key role of the Wnt signalling pathway involves the maintenance of stem cell renewal.
  • Somatic mutations in the Wnt pathway components are commonly found in cancer, including over 90% of colorectal cancers.
  • Wnt pathway activation leads to inhibition of the β‐catenin destruction complex consisting of APC, Axin, CK1α and GSK3.
  • Mutations in the tumour suppressor, adenomatous polyposis coli (APC), lead to Wnt pathway activation.
  • Syndromes caused by germline mutations in Wnt pathway genes include familial adenomatous polyposis (FAP), which results in early polyp development and subsequent colorectal cancer.
  • Wnt pathway drugs have been developed to target receptor activation, β‐catenin degradation and nuclear activation, though currently none of these drugs are FDA approved for patient use.

Keywords: Wnt; cancer; small molecules; biologics; inhibitors; β‐catenin; Axin; APC; tumour suppressor; oncogene

Figure 1. Current model of Wnt signal transduction. Wnt components known to be altered in human cancers are shown in red. Wnt inhibitors are labelled in black. See main text for details.


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Further Reading

Anastas JN and Moon RT (2013) WNT signalling pathways as therapeutic targets in cancer. Nature Reviews Cancer 13: 11–26. DOI: 10.1038/nrc3419.

Clevers H, Loh KM and Nusse R (2014) Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control. Science 346: 1248012. DOI: 10.1126/science.1248012.

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Pinto D and Clevers H (2005) Wnt control of stem cells and differentiation in the intestinal epithelium. Experimental Cell Research 306 (2): 357–363. DOI: 10.1016/j.yexcr.2005.02.022.

Polakis P (2012) Drugging Wnt signalling in cancer. EMBO Journal 31 (12): 2737–2746. DOI: 10.1038/emboj.2012.126.

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Baskir, Rubin S, Hansen, Amanda G, and Lee, Ethan(Apr 2016) Role of the Wnt Signalling Pathway in Cancer. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0025213]