ERK5 negatively regulates tobacco smoke-induced pulmonary epithelial-mesenchymal transition.
ERK5 negatively regulates tobacco smoke-induced pulmonary epithelial-mesenchymal transition.
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DOI：
10.18632/oncotarget.3747
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发表时间：
2015-08-14
期刊：
影响因子：
--
通讯作者：
Zhong C
中科院分区：
文献类型：
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作者：
Liang Z;Xie W;Wu R;Geng H;Zhao L;Xie C;Li X;Huang C;Zhu J;Zhu M;Zhu W;Wu J;Geng S;Zhong C
作为肺癌的主要原因，烟草烟雾（TS）促进肺部肿瘤发生的发生和进展。上皮间质转化（EMT）是细胞恶性转化的关键过程。 ERK5（MAPK 家族中研究较少的成员）在调节 TS 触发的肺 EMT 中的作用尚未得到研究。使用正常人支气管上皮细胞和BALB/c小鼠作为体外和体内TS暴露模型。将正常人支气管上皮细胞暴露于 TS 7 天，可诱导形态变化，增强迁移和侵袭能力，减少上皮标志物表达，增加间充质标志物表达。重要的是，我们首次证明 ERK5 负调节 TS 介导的肺上皮 EMT，这一点可以通过 TS 抑制 ERK5 激活的发现来证明，并且 TS 触发的 EMT 可以通过 ERK5 抑制来模拟，并通过 ERK5 过表达来逆转。在暴露于 TS 12 周的小鼠中进一步证实了 ERK5 对肺 EMT 的负调节作用。综上所述，我们的数据表明 ERK5 负向调节 TS 介导的肺 EMT。这些发现为 TS 相关肺部肿瘤发生的分子机制提供了新的见解，并可能为寻找肺癌干预的潜在靶点开辟新途径。
As the primary cause of lung cancer, tobacco smoke (TS) promotes the initiation and progression of lung tumorigenesis. Epithelial-mesenchymal transition (EMT) is a crucial process involved in cell malignant transformation. The role of ERK5, the lesser studied member of MAPKs family, in regulating TS-triggered pulmonary EMT has not been investigated. Normal human bronchial epithelial cells and BALB/c mice were used as in vitro and in vivo TS exposure models. Exposure of normal human bronchial epithelial cells to TS for 7 days induced morphological change, enhanced migratory and invasive capacities, reduced epithelial marker expression and increased mesenchymal marker expression. Importantly, we demonstrated for the first time that ERK5 negatively regulated TS-mediated lung epithelial EMT, as evidenced by the findings that TS suppressed ERK5 activation, and that TS-triggered EMT was mimicked with ERK5 inhibition and reversed by ERK5 overexpression. The negative regulation of ERK5 on pulmonary EMT was further confirmed in mice exposed to TS for 12 weeks. Taken together, our data suggest that ERK5 negatively regulates TS-mediated pulmonary EMT. These findings provide new insight into the molecular mechanisms of TS-associated lung tumorigenesis and may open up new avenues in the search for potential target of lung cancer intervention.