Signaling by WNT in cancer

Both tumor suppressors and oncogenes have been identified in the so-called canonical WNT pathway, which regulates WNT-dependent transcription by promoting the degradation of beta-catenin in the absence of ligand (reviewed in Polakis, 2012). Loss-of-function mutations in the destruction complex components APC, Axin and AMER1 and gain-of-function mutations in beta-catenin itself cause constitutive signaling and are found in cancers of the intestine, kidney, liver and stomach, among others. WNTs and WNT pathway components are also frequently over- or under-expressed in various cancers, and these changes are correlated with epigenetic regulation of promoter activity. In some contexts, both the canonical and non-canonical WNT signaling, which governs processes such as cell polarity and morphogenesis, may also contribute to tumor formation by promoting cell migration, invasiveness and metastasis.