Wang Tao, Xuan Xiaoyan, Pian Linping, Gao Ping, Hu Hong, Zheng Yuling, Zang Wenqiao, Zhao Guoqiang
Tumour Biol. 2014 Feb;35(2):1193-201. doi: 10.1007/s13277-013-1159-3.
Notch has recently been shown to promote epithelial-to-mesenchymal transition (EMT) by involving in the EMT process that occurs during tumor progression and converts polarized epithelial cells into motile, invasive cells. However, it is still unclear whether the Notch signaling pathway is associated with the regulation of EMT in esophageal carcinoma. The present study explored Notch-1-mediated esophageal carcinoma EC-9706 cell invasion and metastasis by inducing epithelial–mesenchymal transition through Snail. The results demonstrated that the inhibition of Notch-1 expression in the esophageal carcinoma cell line EC-9706 could suppress the occurrence of EMT and at the same time could decrease the invasion and metastasis ability of the EC-9706 cells, indicative of its role in EMT. Snail is a transcriptional repressor of E-cadherin. We found that with the inhibition of Notch-1 expression in the esophageal carcinoma cell line EC-9706, the expression of Snail also decreased. Mechanistic studies showed that the up-expression of Snail in the EC-9706 cells restored the suppression of EMT regulated by Notch-1 inhibition, suggesting the role of Snail in Notch-1-mediated EMT. At the same time, the up-expression of Snail in the EC-9706 cells could also rescue the invasion and metastasis ability inhibited by Notch-1 siRNA. Taken together, our results had revealed that Notch-1 could participate in the invasion and metastasis of esophageal carcinoma through EMT via Snail. This study indicated that Notch-1 might be a useful target for esophageal carcinoma prevention and therapy.
最近研究表明，Notch通过参与肿瘤进展过程中发生的上皮-间质转化（EMT）过程，促使极化上皮细胞转变为具有运动性的侵袭性细胞，从而促进上皮-间质转化。然而，Notch信号通路是否与食管癌中EMT的调控相关仍不清楚。本研究通过Snail诱导上皮-间质转化，探讨Notch-1介导的食管癌EC-9706细胞侵袭和转移。结果表明，抑制食管癌细胞系EC-9706中Notch-1的表达可抑制EMT的发生，同时可降低EC-9706细胞的侵袭和转移能力，表明其在EMT中的作用。Snail是E-钙黏蛋白的转录抑制因子。我们发现，抑制食管癌细胞系EC-9706中Notch-1的表达后，Snail的表达也降低。机制研究表明，EC-9706细胞中Snail的上调恢复了Notch-1抑制所调控的EMT抑制作用，提示Snail在Notch-1介导的EMT中的作用。同时，EC-9706细胞中Snail的上调也可挽救Notch-1 siRNA抑制的侵袭和转移能力。综上所述，我们的结果表明，Notch-1可通过Snail经由EMT参与食管癌的侵袭和转移。本研究表明，Notch-1可能是食管癌预防和治疗的一个有用靶点。
