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

Te Sheng Chang, Kuo Liang Wei, Chung Kuang Lu, Yi Hsing Chen, Ying Tung Cheng, Shui Yi Tung, Cheng Shyong Wu, Ming Ko Chiang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

25 Scopus citations

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.

Original languageEnglish
Article number460
JournalInternational Journal of Molecular Sciences
Volume18
Issue number2
DOIs
StatePublished - 21 02 2017

Bibliographical note

Publisher Copyright:
© 2017 by the authors; Licensee MDPI, Basel, Switzerland.

Keywords

  • CCAR1
  • Gastric cancer
  • Metastasis
  • Wnt signaling
  • β-catenin

Fingerprint

Dive into the research topics of 'Inhibition of CCAR1, a coactivator of β-catenin, suppresses the proliferation and migration of gastric cancer cells'. Together they form a unique fingerprint.

Cite this