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Int. J. Mol. Sci. 2017, 18(2), 460; doi:10.3390/ijms18020460

Inhibition of CCAR1, a Coactivator of β-Catenin, Suppresses the Proliferation and Migration of Gastric Cancer Cells

1
Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Chiayi 61303, Taiwan
2
College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
3
Department of Life Science, National Chung Cheng University, Chiayi 62102, Taiwan
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Anthony Lemarié
Received: 27 October 2016 / Revised: 30 January 2017 / Accepted: 15 February 2017 / Published: 21 February 2017
(This article belongs to the Collection Programmed Cell Death and Apoptosis)
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Abstract

The aberrant activation of Wnt signaling has been implicated in a variety of human cancers, including gastric cancer. Given the current hypothesis that cancer arises from cancer stem cells (CSCs), targeting the critical signaling pathways that support CSC self-renewal appears to be a useful approach for cancer therapy. Cell cycle and apoptosis regulator 1 (CCAR1) is a transcriptional coactivator which has been shown to be a component of Wnt/β-catenin signaling, and which plays an important role in transcriptional regulation by β-catenin. However, the function and clinical significance of CCAR1 in gastric cancer have not been elucidated. Here, we show that elevated CCAR1 nuclear expression correlates with the occurrence of gastric cancer. In addition, RNAi-mediated CCAR1 reduction not only suppressed the cell growth and increased apoptosis in AGS and MKN28 cells, but also reduced the migration and invasion ability of these cells. Furthermore, an in vivo xenograft assay revealed that the expression level of CCAR1 was critical for tumorigenesis. Our data demonstrates that CCAR1 contributes to carcinogenesis in gastric cancer and is required for the survival of gastric cancer cells. Moreover, CCAR1 may serve as a diagnostic marker and a potential therapeutic target. View Full-Text
Keywords: gastric cancer; CCAR1; Wnt signaling; β-catenin; metastasis gastric cancer; CCAR1; Wnt signaling; β-catenin; metastasis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Chang, T.-S.; Wei, K.-L.; Lu, C.-K.; Chen, Y.-H.; Cheng, Y.-T.; Tung, S.-Y.; Wu, C.-S.; Chiang, M.-K. Inhibition of CCAR1, a Coactivator of β-Catenin, Suppresses the Proliferation and Migration of Gastric Cancer Cells. Int. J. Mol. Sci. 2017, 18, 460.

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