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PubMed: 36979874 DOI: 10.3390/biomedicines11030896

IFIT2 Depletion Promotes Cancer Stem Cell-like Phenotypes in Oral Cancer.

Biomedicines 11(3)

Authors: Kuo-Chu Lai, Prabha Regmi, Chung-Ji Liu, Jeng-Fan Lo, Te-Chang Lee

Affiliations

  • Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan.
  • Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan.
  • Division of Hematology and Oncology, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, New Taipei City 23652, Taiwan.
  • Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
  • Department of Oral and Maxillofacial Surgery, Mackay Memorial Hospital, Taipei 10421, Taiwan.
  • Institute of Oral Biology, National Yang Ming Chiao Tung University, Taipei 11221, 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. IFIT2/CD24/CD44 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.

MeSH

Neoplasm Metastasis, Stem Cells, Microscopy, Electron, Scanning Transmission, Mouth Neoplasms, Phenotype

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