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IFN-Induced Transmembrane Protein 1 Promotes Invasion at Early Stage of Head and Neck Cancer Progression

Authors' Affiliations: ¹ Department of Oral and Maxillofacial Pathobiology, Division of Frontier Medical Science and ² Department of Biochemistry, Graduate School of Biomedical Sciences and ³ Center of Oral Clinical Examination, Hiroshima University Hospital, Hiroshima University, Hiroshima, Japan and ⁴ Department of Biochemistry, School of Dentistry at Matsudo, Nihon University, Tokyo, Japan

Requests for reprints: Yasusei Kudo or Takashi Takata, Department of Oral and Maxillofacial Pathobiology, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan. Phone: 81-82-257-5634; Fax: 81-82-257-5619; E-mail: ykudo{at}hiroshima-u.ac.jp or ttakata{at}hiroshima-u.ac.jp.

Purpose: Head and neck squamous cell carcinoma (HNSCC) shows 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 IFN-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 reverse transcription–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, whereas normal cells did not. 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.