This is consistent with earlier reports that implicated aberrant RAS signalling in the control of subcellular localization or protein stability of multiple FOXO isoforms.11, 12, 23, 24, 25, 26, 27 Using the isogenic human colon cancer cells HCT-116 K-RAS WT/G13D and HCT-116 K-RAS WT/−, where the oncogenic K-RASG13D allele has been knocked out by homologous recombination,36 we found that the protein but not mRNA abundance of other FOXO isoforms like FOXO1 and FOXO4 are also downregulated specifically in RAS-mutant human colon cancer cells (Figures 1a and b). This evidence concerns the gene FOXO4 and colonic neoplasm.