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首页> 外文期刊>Oncogene >Interferon-induced transmembrane 3 binds osteopontin in vitro: expressed in vivo IFITM3 reduced OPN expression
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Interferon-induced transmembrane 3 binds osteopontin in vitro: expressed in vivo IFITM3 reduced OPN expression

机译：干扰素诱导的跨膜3体外结合骨桥蛋白：体内表达的IFITM3降低了OPN的表达

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Osteopontin is a secreted, integrin-binding and phosphorylated acidic glycoprotein, which has an important role in tumour progression. We have shown that Wnt, Ets, AP-1, c-jun and β-catenin/Lef-1/Tcf-1 stimulates OPN transcription in rat mammary carcinoma cells by binding to a specific promoter sequence. However, co-repressors of OPN have not been identified. In this study, we have used the bacterial two-hybrid system to isolate cDNA-encoding proteins that bind to OPN and modulate its role in malignant transformation. Using this approach we isolated interferon-induced transmembrane protein 3 gene (IFITM3) as a potential protein partner. We show that IFITM3 and OPN interact in vitro and in vivo and that IFITM3 reduces osteopontin (OPN) mRNA expression, possibly by affecting OPN mRNA stability. Stable transfection of IFITM3 inhibits OPN, which mediates anchorage-independent growth, cell adhesion and cell invasion. Northern blot analysis revealed an inverse mRNA expression pattern of IFITM3 and OPN in human mammary cell lines. Inhibition of IFITM3 by antisense RNA promoted OPN protein expression, enhanced cell invasion by parental benign non-invasive Rama 37 cells, indicating that the two proteins interact functionally as well. We also identified an IFITM3 DNA-binding domain, which interacts with OPN, deletion of which abolished its inhibitive effect on OPN. This work has shown for the first time that IFITM3 physically interacts with OPN and reduces OPN mRNA expression, which mediates cell adhesion, cell invasion, colony formation in soft agar and metastasis in a rat model system.
机译：骨桥蛋白是一种分泌的，整合素结合的，磷酸化的酸性糖蛋白，在肿瘤的进展中具有重要作用。我们已经表明，Wnt，Ets，AP-1，c-jun和β-catenin/ Lef-1 / Tcf-1通过与特定的启动子序列结合来刺激大鼠乳腺癌细胞中的OPN转录。但是，尚未确定OPN的共阻遏物。在这项研究中，我们已经使用细菌双杂交系统来分离与OPN结合并调节其在恶性转化中的作用的cDNA编码蛋白。使用这种方法，我们分离了干扰素诱导的跨膜蛋白3基因（IFITM3）作为潜在的蛋白伴侣。我们表明，IFITM3和OPN在体外和体内相互作用，并且IFITM3减少骨桥蛋白（OPN）mRNA的表达，可能是通过影响OPN mRNA的稳定性。 IFITM3的稳定转染抑制了OPN，OPN介导了不依赖锚定的生长，细胞粘附和细胞侵袭。 Northern印迹分析揭示了人乳腺细胞系中IFITM3和OPN的反向mRNA表达模式。反义RNA对IFITM3的抑制促进了OPN蛋白的表达，增强了父母良性非侵入性Rama 37细胞对细胞的侵袭，表明这两种蛋白在功能上也相互作用。我们还鉴定了一个与OPN相互作用的IFITM3 DNA结合结构域，该结构域的删除取消了其对OPN的抑制作用。这项工作首次表明，IFITM3与OPN发生物理相互作用并降低OPN mRNA表达，从而介导细胞粘附，细胞浸润，软琼脂中的集落形成和大鼠模型系统中的转移。

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