Smad4 loss is a late event during tumor progression and correlates with the development of a metastatic tumor in colon carcinogenesis [2,43], fitting well into a model where Smad4 induced expression of specific keratin types in colon cells may help to maintain the cell to cell junctions through desmosomes and hemidesmosomes and thus supporting an epithelial phenotype. This evidence concerns the gene SMAD4 and metastatic neoplasm.