IFITM1 promotes the invasion at the early stage of head and neck cancer progression
IFITM1 Promotes Invasion of HNSCC Cells
Hatano, Hiroko Hiroshima University
Kudo, Yasusei Hiroshima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Ogawa, Ikuko Hiroshima University
Tsunematsu, Takaaki Hiroshima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Kikuchi, Akira Hiroshima University
Abiko, Yoshimitsu Nihon University
Takata, Takashi Hiroshima University
head and neck cancer
Purpose: Head and neck squamous cell carcinoma (HNSCC), one of the most common types of human cancer, show persistent invasion that frequently leads to local recurrence and distant lymphatic metastasis. However, molecular mechanisms associated with invasion of HNSCC remain poorly understood. We identified Interferon-induced transmembrane protein 1 (IFITM1) as a candidate gene for promoting the invasion of HNSCC by comparing the gene expression profiles between parent and a highly invasive clone. Therefore, we examined the role of IFITM1 in the invasion of HNSCC.
Experimental Design: IFITM1 expression was examined in HNSCC cell lines and cases by RT-PCR and immunohistochemistry. IFITM1 overexpressing and knockdown cells were generated, and the invasiveness of these cells was examined by in vitro invasion assay. Gene expression profiling of HNSCC cells overexpressing IFITM1 versus control cells was examined by microarray.
Results: HNSCC cells expressed IFITM1 mRNA at higher levels, while normal cells did not express. By immunohistochemistry, IFITM1 expression was observed in early invasive HNSCC and invasive HNSCC. Interestingly, IFITM1 was expressed at the invasive front of early invasive HNSCC, and higher expression of IFITM1 was found in invasive HNSCC. In fact, IFITM1 overexpression promoted and IFITM1 knockdown suppressed the invasion of HNSCC cells in vitro. Gene expression profiling of HNSCC cells overexpressing IFITM1 versus control cells revealed that several genes including matrix metalloproteinase were up-regulated in IFITM1 overexpressing cells.
Conclusion: Our findings suggest that IFITM1 plays an important role for the invasion at the early stage of HNSCC progression, and that IFITM1 can be a therapeutic target for HNSCC.
Clinical Cancer Research
The American Association for Cancer Research
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