In conclusion, our findings demonstrate that GATA6 simultaneously induces the expression of genes essential for the growth (REG4) and clonogenicity (LGR5), and that cooperation between the GATA6/REG4 and GATA6/LGR5 pathways is important for the tumorigenicity of colon cancer cells. Here, LGR5 is linked to malignant colon neoplasm.