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Published on: August 23, 2019
Interferon-inducible protein, IFIX, has tumor-suppressive effects in oral squamous cell carcinoma
Shan Wang1,2, Fang Li3, Haixia Fan4
1Department of Oral Pathology, Hospital of Stomatology, The First Affiliated Hospital, Harbin Medical University, Harbin, 150001, People's Republic of China. birchtree20032003@126.com.
Abstract:
IFIX, a newly discovered member of the interferon-inducible HIN-200 family, has been identified as a tumor suppressor in breast cancer; however, the involvement of IFIX in oral cancer are poorly understood. Here, we demonstrate a relationship between the level of IFIX expression and the invasive or migratory abilities of oral squamous cell carcinoma. Higher IFIX expression significantly correlated with clinicopathological parameters such as the histopathological grade of clinical samples. In vitro, IFIX overexpression suppressed the invasiveness of human tongue squamous cell carcinoma CAL-27 cells, and this inhibitory effect was mediated by stabilization of the cytoskeleton through various cytokeratins along with downregulation of paxillin, an intracellular adaptor protein that promotes tumor invasion. This inhibitory effect does not appear to affect the transformation of cancer stem-like cells in this cell culture model. Altogether, these data provide novel insights into the tumor-suppressive function of IFIX, namely, stabilization of the cancer cell cytoskeleton.
Insights
Interferon-inducible HIN-200 family member IFIX suppresses oral cancer invasion by stabilizing the cytoskeleton. Higher IFIX expression correlates with better histopathological grade in oral squamous cell carcinoma patients.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The role of IFIX (interferon-inducible HIN-200 family) in oral cancer remains unclear.
- IFIX is known as a tumor suppressor in breast cancer.
Purpose of the Study:
- To investigate the function of IFIX in oral squamous cell carcinoma (OSCC).
- To explore the relationship between IFIX expression and OSCC invasiveness and migration.
Main Methods:
- Correlation analysis of IFIX expression with clinicopathological parameters in clinical OSCC samples.
- In vitro studies using human tongue squamous cell carcinoma CAL-27 cells with IFIX overexpression.
- Analysis of cytoskeletal proteins (cytokeratins) and paxillin expression.
Main Results:
- Higher IFIX expression correlated significantly with histopathological grade in OSCC.
- IFIX overexpression suppressed invasiveness and migration of CAL-27 cells.
- IFIX-mediated suppression involved cytoskeleton stabilization via cytokeratins and paxillin downregulation.
- IFIX did not affect cancer stem-like cell transformation in this model.
Conclusions:
- IFIX exhibits tumor-suppressive functions in oral cancer.
- IFIX stabilizes the cancer cell cytoskeleton, thereby inhibiting invasion and migration.
- IFIX represents a potential therapeutic target for oral cancer.
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