Induction of Slug by Chronic Exposure to Single-Walled Carbon Nanotubes Promotes Tumor Formation and Metastasis.
Induction of Slug by Chronic Exposure to Single-Walled Carbon Nanotubes Promotes Tumor Formation and Metastasis.
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通过长期暴露于单壁碳纳米管来诱导SLUG促进肿瘤的形成和转移。
DOI：
10.1021/acs.chemrestox.7b00049
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发表时间：
2017-07-17
影响因子：
4.1
通讯作者：
Rojanasakul Y
中科院分区：
文献类型：
--
作者：
Wang P;Voronkova M;Luanpitpong S;He X;Riedel H;Dinu CZ;Wang L;Rojanasakul Y
碳纳米管 (CNT) 是一类主要的工程纳米材料，广泛应用于各个领域。然而，由于其潜在的致癌性，它们的使用越来越受到关注。越来越多的证据表明，某些类型的碳纳米管在动物模型中具有致癌性或促肿瘤作用。然而，潜在的分子和细胞机制尚不清楚。在这里，我们报告，长期暴露于单壁（SW）碳纳米管会导致人肺上皮细胞中诱导Slug的诱导，Slug是诱导上皮-间质转化（EMT）的关键转录因子。我们发现，SWCNT 诱导的 Slug 上调在暴露于 SWCNT 的细胞的侵袭性表型中发挥着关键作用，其中包括增加细胞迁移、侵袭和不依赖贴壁的细胞生长。我们的体内研究还表明，SWCNT 诱导的 Slug 上调和 EMT 激活在肿瘤形成和转移中发挥着关键作用。我们的研究结果说明了 CNT 诱导的 Slug 上调、EMT 激活与肿瘤形成和转移之间的直接联系，并强调了 CNT 诱导的 Slug 上调作为未来风险评估和预防 CNT 相关疾病的目标的潜力。
Carbon nanotubes (CNTs) represent a major class of engineered nanomaterials that are being used in diverse fields. However, their use has increasingly become a concern because of their carcinogenic potential. Accumulating evidence has demonstrated that certain types of CNTs are carcinogenic or tumor-promoting in animal models. However, the underlying molecular and cellular mechanisms are unclear. Here, we report that chronic exposure to single-walled (SW) CNTs results in the induction of Slug, a key transcription factor that induces an epithelial–mesenchymal transition (EMT), in human lung epithelial cells. We show that SWCNT-induced Slug upregulation plays a critical role in the aggressive phenotype of SWCNT-exposed cells, which includes increased cell migration, invasion, and anchorage-independent cell growth. Our in vivo studies also show that SWCNT-induced Slug upregulation and EMT activation play a pivotal role in tumor formation and metastasis. Our findings illustrate a direct link between CNT-induced Slug upregulation, EMT activation, and tumor formation and metastasis, and they highlight the potential of CNT-induced Slug upregulation as a target for future risk assessment and prevention of CNT-associated diseases.
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影响因子：
10
作者：
Luanpitpong S;Wang L;Castranova V;Rojanasakul Y
通讯作者：
Rojanasakul Y
影响因子：
4
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11.5
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影响因子：
5
作者：
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Rojanasakul Y
影响因子：
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作者：
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通讯作者：
Lokshin AE