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DEP-1 protein tyrosine phosphatase inhibits proliferation and migration of colon carcinoma cells and is upregulated by protective nutrients

Oncogene volume 25, pages 6319–6324 (2006)Cite this article

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.

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Acknowledgements

This work was supported by grants from the German Federal Ministry of Research and Education (BMBF), Grant 01EA0503 (to FDB and BP-Z), and by the Collaborative Research Center of the Deutsche Forschungsgemeinschaft SFB604, Project A1 (to FDB).

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Authors and Affiliations

  1. Institute of Molecular Cell Biology, Medical Faculty, Friedrich Schiller University, Jena, Germany

    K K Balavenkatraman, E Jandt & F D Böhmer

  2. Institute of Biochemistry I, Medical Faculty, Friedrich Schiller University, Jena, Germany

    K Friedrich

  3. Department of Nutritional Toxicology, Institute for Nutrition, Friedrich Schiller University, Jena, Germany

    T Kautenburger & B L Pool-Zobel

  4. Cancer Center Karolinska, Karolinska Institute, Stockholm, Sweden

    A Östman

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  1. K K Balavenkatraman
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  5. B L Pool-Zobel
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Correspondence to F D Böhmer.

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Balavenkatraman, K., Jandt, E., Friedrich, K. et al. DEP-1 protein tyrosine phosphatase inhibits proliferation and migration of colon carcinoma cells and is upregulated by protective nutrients. Oncogene 25, 6319–6324 (2006). https://doi.org/10.1038/sj.onc.1209647

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