1. ¹Institute of Molecular Cell Biology, Medical Faculty, Friedrich Schiller University, Jena, Germany
2. ²Institute of Biochemistry I, Medical Faculty, Friedrich Schiller University, Jena, Germany
3. ³Department of Nutritional Toxicology, Institute for Nutrition, Friedrich Schiller University, Jena, Germany
4. ⁴Cancer Center Karolinska, Karolinska Institute, Stockholm, Sweden

Correspondence: Dr F-D Böhmer, Institute of Molecular Cell Biology, Medical Faculty, Friedrich Schiller University, Drackendorfer Str. 1, D-07747 Jena, Germany. E-mail: i5frbo@rz.uni-jena.de

Received 17 November 2005; Revised 14 March 2006; Accepted 27 March 2006; Published online 8 May 2006.

Abstract

The transmembrane protein-tyrosine phosphatase (PTP) DEP-1 (density-enhanced phosphatase) is a candidate tumor suppressor in the colon epithelium. We have explored the function of DEP-1 in colon epithelial cells by inducible re-expression in a DEP-1-deficient human colon cancer cell line. Density-enhanced phosphatase-1 re-expression led to profound inhibition of cell proliferation and cell migration, and was associated with cytoskeletal rearrangements. These effects were dependent on the PTP activity of DEP-1 as they were not observed with cells expressing the catalytically inactive DEP-1 C1239S variant. shRNA-mediated suppression of DEP-1 in a colon epithelial cell line with high endogenous DEP-1 levels enhanced proliferation, further supporting the antiproliferative function of DEP-1. Nutrients, which are considered to be chemoprotective with respect to colon cancer development, including butyrate, green tea and apple polyphenols, had the capacity to elevate transcription of endogenous DEP-1 mRNA and expression of DEP-1 protein. Upregulation of DEP-1 expression, and in turn inhibition of cell growth and migration may present a previously unrecognized mechanism of chemoprevention by nutrients.