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ICAT inhibits glioblastoma cell proliferation by suppressing Wnt/β-catenin activity
Kailiang Zhang1, Shanjun Zhu1, Yanwei Liu2
1Department 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.
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.
Insights
Inhibitor of β-catenin and T-cell factor (ICAT) acts as a tumor suppressor in human glioma. Lower ICAT expression correlates with higher glioma grade and poorer patient survival, indicating its therapeutic potential.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- The Wnt/β-catenin signaling pathway is crucial in development and cancer.
- Inhibitor of β-catenin and T-cell factor (ICAT) negatively regulates this pathway.
- ICAT's role in human glioma was previously uncharacterized.
Purpose of the Study:
- To investigate the expression and function of ICAT in human glioma.
- To determine ICAT's potential as a tumor suppressor in glioma.
Main Methods:
- Analysis of ICAT expression in 305 human glioma tissues.
- In vitro studies using transfected glioma cells (Western blotting, MTT assay, flow cytometry, invasion assays).
- In vivo evaluation using a glioblastoma xenograft model.
Main Results:
- Negative ICAT expression was associated with higher glioma grade and reduced patient survival.
- ICAT overexpression inhibited glioma cell proliferation and invasion.
- ICAT induced apoptosis and cell cycle arrest in glioma cells.
- ICAT slowed tumor growth in vivo.
Conclusions:
- ICAT functions as a tumor suppressor in human glioma.
- ICAT expression levels correlate with glioma aggressiveness and patient prognosis.
- ICAT represents a potential therapeutic target for glioma treatment.
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