E-cadherin molecules are cell-cell molecular connectors, but also act attaching cell surface to the cytoskeleton through catenin’s and additional partner proteins. Its main function is to regulate cellular adhesion and motility, and therefore acts as an invasion suppressor system. Its role is crucial in the induction and maintenance of cell polarity and differentiation, and in the organization and maintenance of tissue architecture. Downregulation or loss of its function is associated with an invasive and aggressive phenotype in many types of human cancers. In alterations of animal development, E-cadherin dysfunction influence in premature lethality or epidermal barrier and immunity defects. However, new hypothesis over its promoter role in tissue invasion is on focus. In addition to its tumor suppressor role, E-cadherin is a guiding molecule in collective cell migration increasing the metastasis risk during in vivo tumorigenesis. This E-cadherin function explains the retention of the functional E-cadherin expression, and that the epithelial-mesenchymal transition (EMT) is not required for the metastasis occurrence. However, like a switch, in some tumoral environments E-cadherin post-translational modifications may cause cell cluster migration. Like in development, in certain in vivo tumoral contexts, E-cadherin apparently involves signaling rather than cell contact formation. In this report, we explore the possibility of a novel role of thyroid hormones (THs) in the signal via E-cadherin-catenins, this not only should be involved in development and homeostasis, but also in cancer susceptibility of gastrointestinal tract.