Loss of APC function results in increasedlevels of β-catenin, a key effector of Wnt signaling that interacts withthe HMG-box DNA-binding factor TCF4 (TCF7L2) to drive target gene transcription.Activating mutations in CTNNB1 (β-catenin; see Glossary,Box 1), or inother Wnt signaling activators (e.g. RSPO2/3) (Morin et al., 1997; Seshagiri et al., 2012) can alsohyperactivate Wnt signaling in CRC, as can inactivating mutations in Wntrepressors (e.g. AXIN2, SFRP1,RNF43 or ZNRF3) (Liu et al., 2000; Suzuki et al., 2004; Koo et al., 2012). Here, TCF4 is linked to colorectal carcinoma.