Abstract 5753: Inhibition of CCAR1, a coactivator of β-catenin, suppresses the proliferation and migration of gastric cancer cells

Abstract

Abstract Given a current hypothesis that cancer arises from cancer stem cells (CSCs), targeting key signaling pathways that support CSC self-renewal appears to be a useful approach to cancer therapy. Derranged expression of Wnt signaling is among the major pathways implicated in regulating the stenmess properties of a variety of human cancers, including gastric cancer. 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 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 the 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 gastric cell lines AGS and MKN28, but also reduced the migration and invasion ability of these cells. Furthermore, 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. Citation Format: Te-Sheng Chang, Chung-Kuang Lu, Kuo-Liang Wei, Yi-Hsing Chen, Ying-Tung Cheng, Shui-Yi Tung, Cheng-Shyong Wu, Ming-Ko Chiang. Inhibition of CCAR1, a coactivator of β-catenin, suppresses the proliferation and migration of gastric cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5753. doi:10.1158/1538-7445.AM2017-5753