Cigarette smoke induced urocystic epithelial mesenchymal transition via MAPK pathways.
Cigarette smoke induced urocystic epithelial mesenchymal transition via MAPK pathways.
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香烟烟雾通过 MAPK 途径诱导尿囊上皮间质转化
DOI：
10.18632/oncotarget.14456
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发表时间：
2017-01-31
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：
Yu D;Geng H;Liu Z;Zhao L;Liang Z;Zhang Z;Xie D;Wang Y;Zhang T;Min J;Zhong C
吸烟已被证明是膀胱癌的主要危险因素。上皮-间质转化（EMT）是癌症发展的关键过程。MAPK通路在调节香烟烟雾引发的尿囊EMT中的作用仍有待阐明。采用人正常尿路上皮细胞和BALB/c小鼠作为体外和体内香烟烟雾暴露模型。人正常尿路上皮细胞暴露于香烟烟雾诱导形态学改变，增强迁移和侵袭能力，减少上皮标志物表达和增加间充质标志物表达，沿着MAPK途径的激活。此外，我们发现ERK 1/2和p38抑制剂，而不是JNK抑制剂，有效地减弱香烟烟雾诱导的尿囊EMT。重要的是，在暴露于CS 12周的小鼠中进一步证实了ERK 12和p38通路在香烟烟雾触发的尿囊EMT中的调节功能。这些发现可以为香烟烟雾相关膀胱癌发展的分子机制及其潜在干预提供新的见解。
Cigarette smoke has been shown to be a major risk factor for bladder cancer. Epithelial-mesenchymal transition (EMT) is a crucial process in cancer development. The role of MAPK pathways in regulating cigarette smoke-triggered urocystic EMT remains to be elucidated. Human normal urothelial cells and BALB/c mice were used as in vitro and in vivo cigarette smoke exposure models. Exposure of human normal urothelial cells to cigarette smoke induced morphological change, enhanced migratory and invasive capacities, reduced epithelial marker expression and increased mesenchymal marker expression, along with the activation of MAPK pathways. Moreover, we revealed that ERK1/2 and p38 inhibitors, but rather JNK inhibitor, effectively attenuated cigarette smoke-induced urocystic EMT. Importantly, the regulatory function of ERK1/2 and p38 pathways in cigarette smoke-triggered urocystic EMT was further confirmed in mice exposed to CS for 12 weeks. These findings could provide new insight into the molecular mechanisms of cigarette smoke-associated bladder cancer development as well as its potential intervention.