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Cancer Lett. 2015 Feb 1;357(1):404-411. doi: 10.1016/j.canlet.2014.11.047. Epub 2014 Nov 27.

ICAT inhibits glioblastoma cell proliferation by suppressing Wnt/β-catenin activity.

Author information

1
Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, China; Chinese Glioma Cooperative Group (CGCG), 6 Tiantanxi Li, Beijing 100050, China.
2
Chinese Glioma Cooperative Group (CGCG), 6 Tiantanxi Li, Beijing 100050, China; Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, 6 Tiantanxi Li, Beijing 100050, China.
3
Department of Medicine, Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States.
4
School of Materials Science and Engineering, Tianjin University, Tianjin 300072, China.
5
Chinese Glioma Cooperative Group (CGCG), 6 Tiantanxi Li, Beijing 100050, China; Department of Medicine, Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States.
6
Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, China; Chinese Glioma Cooperative Group (CGCG), 6 Tiantanxi Li, Beijing 100050, China. Electronic address: superhanlei@hotmail.com.
7
Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, China; Chinese Glioma Cooperative Group (CGCG), 6 Tiantanxi Li, Beijing 100050, China. Electronic address: kang97061@gmail.com.

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.

KEYWORDS:

Glioma; ICAT; Proliferation; Wnt; β-catenin

PMID:
25434796
DOI:
10.1016/j.canlet.2014.11.047
[Indexed for MEDLINE]

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