This, together with the repression of the expression of the stem cell-associated genes ASCL2 and LGR4, which characterize the WNT-dependency of intestinal crypts, adenomas and early local carcinomas (Barker et al, 2007; van der Flier et al, 2007; Zhu et al, 2012), raises the possibility that SOX12 and TMED3 sustain a WNT-dependent, large-spheroid-forming, clonogenic stem cell that is non-metastatic. Here, LGR4 is linked to adenoma.