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Updated: Aug 5, 2025
Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics
Published on: May 11, 2016
IFIT2 Depletion Promotes Cancer Stem Cell-like Phenotypes in Oral Cancer
Kuo-Chu Lai1,2,3, Prabha Regmi4, Chung-Ji Liu5
1Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan.
Abstract:
(1) Background: Cancer stem cells (CSCs) are a small cell population associated with chemoresistance, metastasis and increased mortality rate in oral cancer. Interferon-induced proteins with tetratricopeptide repeats 2 (IFIT2) depletion results in epithelial to mesenchymal transition, invasion, metastasis, and chemoresistance in oral cancer. To date, no study has demonstrated the effect of IFIT2 depletion on the CSC-like phenotype in oral cancer cells. (2) Methods: Q-PCR, sphere formation, Hoechst 33,342 dye exclusion, immunofluorescence staining, and flow cytometry assays were performed to evaluate the expression of the CSC markers in IFIT2-depleted cells. A tumorigenicity assay was adopted to assess the tumor formation ability. Immunohistochemical staining was used to examine the protein levels of IFIT2 and CD24 in oral cancer patients. (3) Results: The cultured IFIT2 knockdown cells exhibited an overexpression of ABCG2 and CD44 and a downregulation of CD24 and gave rise to CSC-like phenotypes. Clinically, there was a positive correlation between IFIT2 and CD24 in the patients. IFIT2high/CD24high/CD44low expression profiles predicted a better prognosis in HNC, including oral cancer. The TNF-α blockade abolished the IFIT2 depletion-induced sphere formation, indicating that TNF-α may be involved in the CSC-like phenotypes in oral cancer. (4) Conclusions: The present study demonstrates that IFIT2 depletion promotes CSC-like phenotypes in oral cancer.
Insights
Interferon-induced proteins with tetratricopeptide repeats 2 (IFIT2) depletion promotes cancer stem cell (CSC)-like phenotypes in oral cancer. This suggests IFIT2 plays a crucial role in regulating CSC characteristics and potential therapeutic targeting.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Cancer stem cells (CSCs) drive oral cancer progression, chemoresistance, and metastasis.
- Interferon-induced proteins with tetratricopeptide repeats 2 (IFIT2) depletion is linked to oral cancer invasion and chemoresistance.
- The impact of IFIT2 depletion on CSC phenotypes in oral cancer remains unexplored.
Purpose of the Study:
- To investigate the effect of IFIT2 depletion on CSC-like phenotypes in oral cancer cells.
- To explore the correlation between IFIT2 expression and CSC markers in oral cancer patients.
- To elucidate the role of TNF-α in IFIT2 depletion-induced CSC phenotypes.
Main Methods:
- Quantitative PCR (Q-PCR) and flow cytometry to assess CSC marker expression (ABCG2, CD44, CD24) in IFIT2-depleted cells.
- Sphere formation and Hoechst 33,342 dye exclusion assays to evaluate CSC-like properties.
- Tumorigenicity assays and immunohistochemical staining to analyze tumor formation and protein levels in patient samples.
Main Results:
- IFIT2 depletion led to overexpression of ABCG2 and CD44, and downregulation of CD24, inducing CSC-like phenotypes.
- A positive correlation between IFIT2 and CD24 expression was observed in oral cancer patients.
- IFIT2high/CD24high/CD44low expression predicted a better prognosis in head and neck cancer (HNC).
- TNF-α blockade inhibited IFIT2 depletion-induced sphere formation, implicating TNF-α in CSC phenotypes.
Conclusions:
- IFIT2 depletion promotes CSC-like phenotypes in oral cancer.
- IFIT2 expression levels, particularly in conjunction with CD24 and CD44, can serve as prognostic markers for HNC.
- TNF-α signaling pathway is potentially involved in the development of CSC-like phenotypes induced by IFIT2 depletion.
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