Fig. 5

T3-control model of E-cadherin─β-catenin complex on gastrointestinal epithelial cells. THs and RTs function in cell proliferation, differentiation and apoptosis is not homogenous, because it depends strongly on physio-pathological context; that is, the cell-type, ontogeny (progenitor or differentiated cell) and health (normal or tumoral cell). However, it is possible to postulate that, while T3 induces epithelial basal cell proliferation via EGF-EGFR and cAMP-PKA signaling, T3 activates transcription of E-cadherin, β- and α-catenin genes in epithelial cells programmed to differentiate on pre-adult gut epithelia cells and inhibiting their EGF-EGFR dependent proliferative signal, as well as inhibiting their TH-integrin αvβ3 dependent migratory signals. In addition, because E-cadherin increases β-catenin sequestration at the plasma membrane, it then promotes cell differentiation by diminishing the β-catenin/TCF complex pool. At the same time, TSH-TSHR (receptor) signaling via cAMP stabilizes the assembly and retention of E-cadherin at the cell surface. TRα1 binds to β-catenin gene-intron 1-TRE (TRE-int1) in the intestine, increasing its expression via TH-binding. In parallel, TRα1 positively regulates the proliferation-controlling genes such as type D cyclins and c-myc, which are known targets of the Wnt/β-catenin. Increase of β-catenin/Tcf4, in turn, reduces the TRα1 transcriptional activity on its target genes. On the other hand, CTNNB1 transrepression is mediated by binding of the TRβ-RXR complexes to promoter TREs