Wang Peng, Voronkova Maria, Luanpitpong Sudjit, He Xiaoqing, Riedel Heimo, Dinu Cerasela Z, Wang Liying, Rojanasakul Yon
Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine, Mahidol University , Bangkok 10700, Thailand.
Health Effects Laboratory Division, National Institute for Occupational Safety and Health , Morgantown, West Virginia 26505, United States.
Chem Res Toxicol. 2017 Jul 17;30(7):1396-1405. doi: 10.1021/acs.chemrestox.7b00049. Epub 2017 Jun 20.
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.
碳纳米管（CNTs）是一类主要的工程纳米材料，正在被应用于多个领域。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，其潜在的分子和细胞机制尚不清楚。在此，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关键转录因子Slug的诱导，Slug可诱导上皮-间质转化（EMT）。我们表明，SWCNT诱导的Slug上调在暴露于SWCNT的细胞的侵袭性表型中起关键作用，这包括细胞迁移、侵袭增加以及非锚定依赖性细胞生长。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起关键作用。我们的研究结果阐明了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，并突出了CNT诱导的Slug上调作为未来风险评估和预防CNT相关疾病靶点的潜力。
