PHOSPHORYLATION OF BETA-CATENIN AND EPIDERMAL GROWTH-FACTOR RECEPTOR BY INTESTINAL TREFOIL FACTOR

Intestinal trefoil factor (TFF3) is a member of the trefoil family of peptides, which are constitutively expressed in the gastrointestinal t ract. TFF3 has been shown to promote migration of intestinal epithelia l cells in vitro and to enhance epithelial restitution in vivo. In the present study, we show that the stimulatory effect of TFF3 on the mig ration of HT29 colonic carcinoma cells requires the perturbation of E- cadherin function, a calcium-dependent cell-cell adhesion molecule in epithelia. A rapid (<1 minute) and specific tyrosine phosphorylation o f beta-catenin and epidermal growth factor receptor was detected in ce lls treated with recombinant rat TFF3. No phosphorylation of E-cadheri n or alpha-catenin was detected. Tyrosine phosphorylation of beta-cate nin was associated with reduced membranous E-cadherin expression, pert urbation of intercellular adhesion, and promotion of cell motility. Th ese results suggest that TFF3 enhances cell migration through modulati on of E-cadherin/catenin complex function. Tyrosine phosphorylation of beta-catenin and epidermal growth factor receptor seems to be involve d in this process.