p38 MAPK mediates epithelial-mesenchymal transition by regulating p38IP and Snail in head and neck squamous cell carcinoma
p38 MAPK mediates epithelial-mesenchymal transition by regulating p38IP and Snail in head and neck squamous cell carcinoma
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DOI：
10.1016/j.oraloncology.2016.06.010
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发表时间：
2016-09-01
期刊：
影响因子：
4.8
通讯作者：
St John, Maie
中科院分区：
文献类型：
--
作者：
Lin, Yuan;Mallen-St Clair, Jon;St John, Maie
背景：在本研究中，我们探讨了p38-p38IP信号在炎症诱导的头颈部鳞状细胞癌上皮向间充质转化中的作用。方法：采用定量RT-PCR、蛋白质印迹分析、球体模型和免疫组织化学染色等方法。结果：p38抑制剂处理和p38shRNA处理的头颈部鳞状细胞癌细胞株E-钙粘蛋白mRNA表达显著上调，Snail的mRNA表达显著降低。P38与组蛋白SPT3-TAF9-GCN5乙酰转移酶(STAGA)的亚基p38IP结合并稳定，导致Snail转录增强。在椭圆形模型中，p38shRNA HNSCC细胞株表现出侵袭性较小的表型。在临床HNSCC组织中，p38相互作用蛋白(P38IP)的表达明显高于癌旁正常组织。结论：p38-p38IP参与了蜗牛诱导的HNSCC中E-钙粘蛋白的下调和细胞侵袭。(C)2016爱思唯尔有限公司。保留所有权利。
Background: In the present study, we investigated the role of p38-p38IP signaling in the inflammation-induced promotion of epithelial-to-mesenchymal transition (EMT) in Head and Neck Squamous Cell Carcinoma (HNSCC).Methods: Quantitative RT-PCR, western blot analysis, spheroid modeling and immunohistochemical staining of human HNSCC tissue sections were used.Results: p38 inhibitor treated and p38 shRNA HNSCC cell lines demonstrate a significant upregulation in E-cadherin mRNA and a decrease in the mRNA expression of Snail. p38 binds to and stabilizes p38IP, a subunit of histone SPT3-TAF9-GCN5 acetyltransferase (STAGA), resulting in enhanced transcription of Snail. p38 shRNA HNSCC cell lines show a less invasive phenotype in a spheroid model. In clinical HNSCC samples, p38 interacting protein (p38IP) is significantly increased compared to adjacent normal tissue. An inverse relationship between p38, p38IP and E-cadherin is demonstrated.Conclusions: Herein we provide the first report that p38-p38IP is required for the Snail-induced E-cadherin down-regulation and cell invasion in HNSCC. (C) 2016 Elsevier Ltd. All rights reserved.