ICAT inhibits glioblastoma cell proliferation by suppressing Wnt/β-catenin activity. Issue 1 (1st February 2015)

• Record Type: Journal Article
• Authors: Zhang, Kailiang; Zhu, Shanjun; Liu, Yanwei; Dong, Xiaoqun; Shi, Zhendong; Zhang, Anling; Liu, Chaoyong; Chen, Luyue; Wei, Jianwei; Pu, Peiyu; Zhang, Jianning; Jiang, Tao; Han, Lei; Kang, Chunsheng
• Is Part Of: Cancer letters. Volume 357:Issue 1(2015)
• Page Start: 404
• Page End: 411
• Publication Date: 2015-02-01
• Subjects: ICAT -- Glioma -- Wnt -- β-catenin -- Proliferation; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2014.11.047
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: ICAT is downregulated in high-grade glioma samples. ICAT restoration inhibits glioblastoma cell proliferation, invasion and induces glioblastoma cell apoptosis. ICAT regulates Wnt/β-catenin signaling. Therapeutic potential of ICAT in a glioblastoma xenograft model. ICAT correlates with IDH1 mutation and TCGA subtype. Abstract: Inhibitor of β-catenin and T-cell factor (ICAT) is a key component of Wnt/β-catenin signaling. ICAT blocks the formation of the β-catenin/TCF complex and has been demonstrated to be involved in embryonic development and carcinogenesis. As an inhibitor of canonical Wnt signaling, ICAT was presumed to be a tumor-suppressor gene. However, the ICAT functions in human glioma remain unknown. In this study, we evaluated the expression of ICAT in 305 human glioma tissues and found that negative ICAT expression correlated with higher grade glioma and poor survival in patients with glioma. Then we transfected glioma cells with ICAT plasmid. Western blotting showed an increased ICAT protein expression level in glioma cells. MTT assay, flow cytometry and cell invasion assay were used to detect cell proliferation, cell cycle distribution, apoptosis and invasion. Our studies confirmed that ICAT inhibits glioma cell proliferation and invasion, and it induces cell apoptosis and cell cycle progression arrest. Besides, ICAT slowed down tumor growth in a glioblastoma xenograft model. Therefore, our study demonstrates that ICAT may serve as a tumor-suppressor in human glioma suggesting a promising direction for targeting therapy in glioma.