SMAD4 and adenoma: The dose dependency of TGF-β1 ligand supply with respect to adenoma organoid cell growth phenotype has not been previously described to our knowledge, but may contribute functionally to the manifestation of differential phenotypes with Smad4 LOF; at a given dose, pathway gene expression positively modifies differentiation and EMT function, but at the same time there is resistance to cell death and cell cycle arrest.