核转录因子OCT4在维持癌细胞增殖和肿瘤干细胞自我更新、阻止癌细胞分化等过程中起重要作用。我们在前期研究中发现，食管癌中有很少部分的癌细胞OCT4呈阳性表达，可引起癌细胞上皮间质转化（EMT），阻止癌细胞发生失巢凋亡，与癌细胞高增殖转移活性密切相关；同时细胞学实验显示，高表达OCT4能够上调血管内皮生长因子C (VEGF-C)表达并促进肿瘤发生EMT；此外，高表达VEGF-C同样可以诱导食管癌细胞发生EMT，但相关分子机制不明。据此，我们推测OCT4可能通过在转录水平对VEGF-C表达进行调控，促进食管肿瘤细胞发生EMT。本项目拟在前期研究的基础上通过ChIP、荧光素酶报告基因、转基因或基因沉默、动物成瘤转移并结合临床统计分析进一步明确其信号通路，从而加深对OCT4调控癌细胞增殖分子机制的了解。本项研究具有较强的创新性，如获成功，将为食管癌生物靶向治疗提供新的有效靶标。

Nuclear transcription factor OCT4 plays an important role in maintaining cancer cell proliferation,preventing cancer cells from differentiation, and especially promoting cancer stem cells to renew themselves. In our previous study, we found that there was a little OCT4 positive cells in esophageal cancer, which can cause cancer cells to present the process of Epitheilal-mesenchymal transition (EMT), and prevent cancer cells from anoikis. Cytology experiments have showed that OCT4 could increase vascular endothelial growth factor C (VEGF-C) expression and promote esophageal squamous cell carcinoma (ESCC) EMT. Moreover, over-expression of VEGF - C could induce EMT in ESCC cells.Therefore, we hypothesized that OCT4 might promote ESCC EMT and metastasis via OCT4 mediated up-regulation of VEGF-C expression.In this project, we will evaluate the role of OCT4/ VEGF-C in the EMT of ESCC by multiple approaches including clinical investigation ,luciferase reporter assay, ChIP, adenovirus mediated gene delivery, and metastasis assay in NOD/SCID mice. It will help us to establish effective gene treatment strategies targeting to esophageal carcinoma. The study can provides theoretical basis and efficiency target genes for esophageal carcinoma biological therapy.