Thus FBW7 heterozygosity results in increased Hes5 expression both in human colorectal tumours and in the APCmin;Fbw7ΔG/+ mouse model, suggesting that the NICD/HES5/FBW7β positive feedback loop is the molecular mechanism that underlies FBW7 haploinsufficiency in tumour suppression. Here, HES5 is linked to colorectal neoplasm.