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Dan Liu, Iman
El-Hariry, Anastasios J. Karayiannakis, Jonathan Wilding, Rebecca Chinery,
Witold Kmiot, Pierre D. McCrea, William J. Gullick, and Massimo Pignatelli
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Divisions
of Investigative Science (DL, IE-H, JW, MP) and Surgery (AJK, WK), Imperial
College of Science, Technology, and Medicine, and Epithelial Research Unit
(RC), Royal College of Surgeons, London, United Kingdom; Department of Biochemistry
and Molecular Biology (PM), University of Texas, MD Anderson Cancer Center,
Houston, Texas; and Receptor Biology Laboratory (WJG), Imperial Cancer Research
Fund, Molecular Oncology Unit, Hammersmith Hospital, London, United Kingdom |
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Intestinal trefoil factor
(TFF3) is a member of the trefoil family of peptides, which are constitutively
expressed in the gastrointestinal tract. TFF3 has been shown to promote
migration of intestinal epithelial cells in vitro and to enhance epithelial
restitution in vivo. In the present study, we show that the stimulatory
effect of TFF3 on the migration 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
of [beta]-catenin and epidermal growth factor receptor was detected in cells
treated with recombinant rat TFF3. No phosphorylation of E-cadherin or [alpha]-catenin
was detected. Tyrosine phosphorylation of [beta]-catenin was associated
with reduced membranous E-cadherin expression, perturbation of intercellular
adhesion, and promotion of cell motility. These results suggest that TFF3
enhances cell migration through modulation of E-cadherin/catenin complex
function. Tyrosine phosphorylation of [beta]-catenin and epidermal growth
factor receptor seems to be involved in this process. |
