Loss of Coxsackie and adenovirus receptor downregulates alpha-catenin expression.

Abstract

BACKGROUND:

The Coxsackie and adenovirus receptor (CAR) has been shown to inhibit cancer cell proliferation, migration, and invasion. The underlying mechanisms, however, are poorly understood.

METHODS:

The differential gene expression in the human colon cancer cell line DLD1 on RNAi-mediated functional CAR knockdown was analysed using oligo-array technology. Expression of alpha-catenin was determined by quantitative RT-PCR and western blotting. Proliferation, migration, and invasion after CAR knockdown were assessed by in vitro assays, and cell morphology in a three-dimensional context was evaluated using matrigel.

RESULTS:

Oligo-array technology identified alpha-catenin as the strongest downregulated gene after CAR knockdown. Western blotting and quantitative RT-PCR confirmed a reduced alpha-catenin expression after CAR knockdown in DLD1 cells and in the rat intestinal cell line IEC-6. Functionally, both cell lines showed a marked increase in proliferation, migration, and invasion on CAR knockdown. In matrigel, both cell lines formed amorphous cell clusters in contrast to well-organised three-dimensional structures of CAR-expressing vector controls. Ectopic 're'-expression of alpha-catenin in DLD1 and IEC-6 CAR knockdown cells reversed these functional and morphological effects.

CONCLUSION:

These data suggest that an interaction of CAR and alpha-catenin mediates the impact of CAR on cell proliferation, migration, invasion, and morphology.

• Authors: K Stecker, A Koschel, B Wiedenmann, M Anders
• Journal: British journal of cancer (Br J Cancer) Vol. 101 Issue 9 Pg. 1574-9 (Nov 03 2009) ISSN: 1532-1827 [Electronic] England
• PMID: 19773761 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CLMP protein, human
• Clmp protein, rat
• Coxsackie and Adenovirus Receptor-Like Membrane Protein
• Receptors, Virus
• alpha Catenin

Topics

• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Coxsackie and Adenovirus Receptor-Like Membrane Protein
• Down-Regulation
• Gene Expression Regulation
• Humans
• Immunoprecipitation
• Neoplasm Invasiveness
• Receptors, Virus (analysis, physiology)
• alpha Catenin (analysis, genetics, physiology)