Lin Yuan, Mallen-St Clair Jon, Wang Guanyu, Luo Jie, Palma-Diaz Fernando, Lai Chi, Elashoff David A, Sharma Sherven, Dubinett Steven M, St John Maie
Lung Cancer Research Program of the Jonsson Comprehensive Cancer Center, United States; Division of Pulmonary and Critical Care Medicine, Department of Medicine, United States.
Department of Head and Neck Surgery, United States.
Oral Oncol. 2016 Sep;60:81-9. doi: 10.1016/j.oraloncology.2016.06.010. Epub 2016 Jul 15.
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).
Quantitative RT-PCR, western blot analysis, spheroid modeling and immunohistochemical staining of human HNSCC tissue sections were used.
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.
Herein we provide the first report that p38-p38IP is required for the Snail-induced E-cadherin down-regulation and cell invasion in HNSCC.
在本研究中，我们调查了p38-p38IP信号在炎症诱导的头颈部鳞状细胞癌（HNSCC）上皮-间质转化（EMT）促进过程中的作用。
采用定量逆转录聚合酶链反应（qRT-PCR）、蛋白质免疫印迹分析、球体模型构建以及人HNSCC组织切片的免疫组织化学染色。
用p38抑制剂处理的和p38短发夹RNA（shRNA）的HNSCC细胞系显示E-钙黏蛋白mRNA显著上调，Snail的mRNA表达下降。p38与组蛋白SPT3-TAF9-GCN5乙酰转移酶（STAGA）的一个亚基p38IP结合并使其稳定，导致Snail转录增强。p38 shRNA的HNSCC细胞系在球体模型中显示出侵袭性较小的表型。在临床HNSCC样本中，与相邻正常组织相比，p38相互作用蛋白（p38IP）显著增加。p38、p38IP和E-钙黏蛋白之间呈负相关。
在此我们首次报道，p38-p38IP是HNSCC中Snail诱导的E-钙黏蛋白下调和细胞侵袭所必需的。
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