Specificity protein 1 regulates fascin expression in esophageal squamous cell carcinoma as the result of the epidermal growth factor/extracellular signal-regulated kinase signaling pathway activation
Specificity protein 1 regulates fascin expression in esophageal squamous cell carcinoma as the result of the epidermal growth factor/extracellular signal-regulated kinase signaling pathway activation
复制标题
由于表皮生长因子/细胞外信号调节激酶信号通路激活，特异性蛋白 1 调节食管鳞状细胞癌中肌成束蛋白的表达
DOI：
10.1007/s00018-010-0382-y
复制
发表时间：
2010-10-01
影响因子：
8
通讯作者：
Xu, Li-Yan
中科院分区：
文献类型：
--
作者：
Lu, Xiao-Feng;Li, En-Min;Xu, Li-Yan
fascin在人类肿瘤中的过度表达与侵袭性临床表型和不良预后相关。然而，肌成束蛋白在癌细胞中表达增加的分子机制在很大程度上是未知的。在此，我们鉴定了位于FSCN 1启动子-70到-60 nt的Sp1结合元件，并验证了Sp1在食管癌细胞中特异性结合该元件。Fascin表达通过Sp1过表达增强，并通过Sp1 RNAi敲低被阻断。特异性抑制ERK 1/2可降低Sp1的磷酸化水平，从而抑制FSCN 1的转录，导致fascin的表达下调。EGF刺激可通过激活ERK 1/2通路和增加Sp1的磷酸化水平来增强fascin的表达。这些数据表明FSCN 1转录可能受到EGF/EGFR信号通路的调节，并可用作预测EGFR抑制剂在癌症治疗中的疗效的可行生物标志物。
The overexpression of fascin in human carcinomas is associated with aggressive clinical phenotypes and poor prognosis. However, the molecular mechanism underlying the increased expression of fascin in cancer cells is largely unknown. Here, we identified a Sp1 binding element located at −70 to −60 nts of theFSCN1promoter and validated that Sp1 specifically bound to this element in esophageal carcinoma cells. Fascin expression was enhanced by Sp1 overexpression and blocked by Sp1 RNAi knockdown. Specific inhibition of ERK1/2 decreased phosphorylation levels of Sp1, and thus suppressed the transcription of theFSCN1, resulting in the down-regulation of fascin. Stimulation with EGF could enhance fascin expression via activating the ERK1/2 pathway and increasing phosphorylation levels of Sp1. These data suggest thatFSCN1transcription may be subjected to the regulation of the EGF/EGFR signaling pathway and can be used as a viable biomarker to predict the efficacy of EGFR inhibitors in cancer therapies.