WNT signalling is activated in some cancers by mutation of adenomatous polyposis coli (APC) or β-catenin (CTNNB1). However, the mechanism of WNT pathway activation in cancers that do not carry these alterations is unclear. Morris et al. found recurrent somatic inactivating mutations in FAT1, which encodes a cadherin-like protein, in several cancer types. Expression of wild-type FAT1 suppressed tumorigenesis, and cancer-associated FAT1 mutations enhanced tumour growth in mice. The authors showed that β-catenin binds FAT1, and that mutated FAT1 promotes the nuclear localization of β-catenin, leading to the expression of WNT–β-catenin target genes.
ORIGINAL RESEARCH PAPER
Morris, L. G. T. et al. Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation. Nature Genet. 27 Jan 2013 (doi:10.1038/ng.2538)
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Seton-Rogers, S. FAT loss lets WNT get active. Nat Rev Cancer 13, 149 (2013). https://doi.org/10.1038/nrc3479
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DOI: https://doi.org/10.1038/nrc3479
