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International Journal of Colorectal Disease

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01-09-2017 | Original Article

γ-Catenin acts as a tumor suppressor through context-dependent mechanisms in colorectal cancer

Authors: Jutta Maria Nagel, Harald Lahm, Andrea Ofner, Burkhard Göke, Frank Thomas Kolligs

Published in: International Journal of Colorectal Disease | Issue 9/2017

Abstract

Purpose

γ-Catenin is a protein closely related to β-catenin. While the overexpression of β-catenin has been linked with impaired prognosis and survival in various malignancies, both oncogenic and tumor suppressor functions have been described for γ-catenin. Thus, its role in cancer remains controversial. In this study, we examined the impact of γ-catenin expression on the malignant potential of colorectal cancer cells.

Methods

γ-Catenin was knocked down by short interfering RNA in the γ-catenin-proficient DLD-1 cell line and stably overexpressed in the γ-catenin-deficient cell line RKO. The effects of these molecular manipulations on the malignant potential of the cell lines were tested in vitro and in vivo in a xenograft tumor model.

Results

γ-Catenin contributed to Wnt signaling independent of the cellular context. Unlike its sister molecule β-catenin, γ-catenin inhibited cellular invasion and anoikis in cells endogenously expressing γ-catenin. In line with this tumor suppressor function, its de novo expression in RKO cells inhibited proliferation via cell cycle arrest. In a xenograft tumor model, overexpression of γ-catenin starkly reduced tumor growth in vivo.

Conclusions

This is the first report demonstrating a tumor-suppressive effect of γ-catenin in colorectal cancer both in vitro and in vivo. Detailed in vitro analysis revealed that effects of γ-catenin differ in γ-catenin proficient and deficient cells, indicating that its function in colorectal cancer is dependent on the cellular context. This finding adds to our understanding of γ-catenin and may have implications for future studies of catenin/Wnt targeted cancer therapies.

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Title: γ-Catenin acts as a tumor suppressor through context-dependent mechanisms in colorectal cancer
Authors: Jutta Maria Nagel
Harald Lahm
Andrea Ofner
Burkhard Göke
Frank Thomas Kolligs
Publication date: 01-09-2017
Publisher: Springer Berlin Heidelberg
Published in: International Journal of Colorectal Disease / Issue 9/2017
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-017-2846-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

γ-Catenin acts as a tumor suppressor through context-dependent mechanisms in colorectal cancer

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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