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

Autor: Balavenkatraman KK; Institute of Molecular Cell Biology, Medical Faculty, Friedrich Schiller University, Jena, Germany., Jandt E, Friedrich K, Kautenburger T, Pool-Zobel BL, Ostman A, Böhmer FD
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2006 Oct 12; Vol. 25 (47), pp. 6319-24. Date of Electronic Publication: 2006 May 08.
DOI: 10.1038/sj.onc.1209647
Abstrakt: 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.
Databáze: MEDLINE