Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Chang, Te-Sheng, Wei, Kuo-Liang, Lu, Chung-Kuang, Chen, Yi-Hsing, Cheng, Ying-Tung, Tung, Shui-Yi, Wu, Cheng-Shyong, Chiang, Ming-Ko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343993/
https://www.ncbi.nlm.nih.gov/pubmed/28230774
http://dx.doi.org/10.3390/ijms18020460
_version_ 1782513471090327552
author Chang, Te-Sheng
Wei, Kuo-Liang
Lu, Chung-Kuang
Chen, Yi-Hsing
Cheng, Ying-Tung
Tung, Shui-Yi
Wu, Cheng-Shyong
Chiang, Ming-Ko
author_facet Chang, Te-Sheng
Wei, Kuo-Liang
Lu, Chung-Kuang
Chen, Yi-Hsing
Cheng, Ying-Tung
Tung, Shui-Yi
Wu, Cheng-Shyong
Chiang, Ming-Ko
author_sort Chang, Te-Sheng
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5343993
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-53439932017-03-16 Inhibition of CCAR1, a Coactivator of β-Catenin, Suppresses the Proliferation and Migration of Gastric Cancer Cells Chang, Te-Sheng Wei, Kuo-Liang Lu, Chung-Kuang Chen, Yi-Hsing Cheng, Ying-Tung Tung, Shui-Yi Wu, Cheng-Shyong Chiang, Ming-Ko Int J Mol Sci Article 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. MDPI 2017-02-21 /pmc/articles/PMC5343993/ /pubmed/28230774 http://dx.doi.org/10.3390/ijms18020460 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chang, Te-Sheng
Wei, Kuo-Liang
Lu, Chung-Kuang
Chen, Yi-Hsing
Cheng, Ying-Tung
Tung, Shui-Yi
Wu, Cheng-Shyong
Chiang, Ming-Ko
Inhibition of CCAR1, a Coactivator of β-Catenin, Suppresses the Proliferation and Migration of Gastric Cancer Cells
title Inhibition of CCAR1, a Coactivator of β-Catenin, Suppresses the Proliferation and Migration of Gastric Cancer Cells
title_full Inhibition of CCAR1, a Coactivator of β-Catenin, Suppresses the Proliferation and Migration of Gastric Cancer Cells
title_fullStr Inhibition of CCAR1, a Coactivator of β-Catenin, Suppresses the Proliferation and Migration of Gastric Cancer Cells
title_full_unstemmed Inhibition of CCAR1, a Coactivator of β-Catenin, Suppresses the Proliferation and Migration of Gastric Cancer Cells
title_short Inhibition of CCAR1, a Coactivator of β-Catenin, Suppresses the Proliferation and Migration of Gastric Cancer Cells
title_sort inhibition of ccar1, a coactivator of β-catenin, suppresses the proliferation and migration of gastric cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343993/
https://www.ncbi.nlm.nih.gov/pubmed/28230774
http://dx.doi.org/10.3390/ijms18020460
work_keys_str_mv AT changtesheng inhibitionofccar1acoactivatorofbcateninsuppressestheproliferationandmigrationofgastriccancercells
AT weikuoliang inhibitionofccar1acoactivatorofbcateninsuppressestheproliferationandmigrationofgastriccancercells
AT luchungkuang inhibitionofccar1acoactivatorofbcateninsuppressestheproliferationandmigrationofgastriccancercells
AT chenyihsing inhibitionofccar1acoactivatorofbcateninsuppressestheproliferationandmigrationofgastriccancercells
AT chengyingtung inhibitionofccar1acoactivatorofbcateninsuppressestheproliferationandmigrationofgastriccancercells
AT tungshuiyi inhibitionofccar1acoactivatorofbcateninsuppressestheproliferationandmigrationofgastriccancercells
AT wuchengshyong inhibitionofccar1acoactivatorofbcateninsuppressestheproliferationandmigrationofgastriccancercells
AT chiangmingko inhibitionofccar1acoactivatorofbcateninsuppressestheproliferationandmigrationofgastriccancercells