IFN-Induced Transmembrane Protein 1 Promotes Invasion at Early Stage of Head and Neck Cancer Progression
IFN-Induced Transmembrane Protein 1 Promotes Invasion at Early Stage of Head and Neck Cancer Progression
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DOI：
10.1158/1078-0432.ccr-07-4761
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发表时间：
2008-10-01
影响因子：
11.5
通讯作者：
Takata, Takashi
中科院分区：
文献类型：
--
作者：
Hatano, Hiroko;Kudo, Yasusei;Takata, Takashi
目的：头颈部鳞状细胞癌(HNSCC)呈持续性侵袭，常导致局部复发和远处淋巴转移。然而，与HNSCC侵袭相关的分子机制仍然知之甚少。通过比较亲本和高侵袭性克隆的基因表达谱，我们确定干扰素诱导的跨膜蛋白1(IFITM1)是促进HNSCC侵袭的候选基因。因此，我们探讨了IFITM1在HNSCC侵袭中的作用。实验设计：采用逆转录-聚合酶链式反应和免疫组织化学方法检测IFITM1在HNSCC细胞系和病例中的表达。通过体外侵袭实验检测细胞的侵袭力。结果：HNSCC细胞高水平表达IFITM1，而正常细胞不表达。免疫组织化学方法观察IFITM1在早期侵袭性HNSCC和侵袭性HNSCC中的表达。有趣的是，IFITM1表达于早期侵袭性HNSCC的侵袭性前沿，且IFITM在侵袭性HNSCC中的表达较高。事实上，IFITM1过表达促进了HNSCC细胞的体外侵袭，而IFITM1基因敲除则抑制了HNSCC细胞的侵袭。高表达IFITM1的HNSCC细胞与对照细胞的基因表达谱显示，在高表达IFITM1的细胞中，包括基质金属蛋白酶在内的多个基因表达上调。结论：IFITM1在HNSCC进展的早期阶段起着重要的侵袭作用，IFITM1可作为HNSCC的治疗靶点。
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 IFITM 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.