Abstract：
The transcription factor forkhead box D3 (FOXD3) is an important member of the FOX family, which can maintain the pluripotent properties of cell clusters, neural crest, and trophoblastic progenitor cells in vivo. It has been shown that FOXD3 could affect proliferation, migration, and angiogenesis of various tumors and its deletion and overexpression in organisms will undoubtedly have important influence on the change of cell fate and the occurrence of tumors. However, the underlying functions and molecular mechanisms of FOXD3 in esophageal squamous cell carcinoma (ESCC) have not been fully clarified. According to the present study, the expression levels and functional roles of FOXD3 were investigated, and its prognostic value and molecular mechanisms in tumorigenesis and progression of ESCC were clarified. The expression level of FOXD3 was significantly downregulated in ESCC tissues and cell lines, and correlated with gender, family history of upper gastrointestinal cancer, TNM stage, depth of invasion, lymph node metastasis, and ESCC patients\' survival. Moreover, FOXD3 inhibited cells migration and invasion as well as participated in TGF-β1 induced epithelial-mesenchymal transition process. Furthermore, a positive correlation between FOXD3 and SMAD family member 7 (SMAD7) was explored in ESCC. FOXD3 could directly bind to promoter regions of SMAD7 gene, leading to transcriptional promotion of SMAD7 in human esophageal cancer cells. Taken together, FOXD3 may play a tumor suppressor role in ESCC and may be applied as a new therapeutic target and prognostic marker for ESCC.
摘要：
转录因子叉头盒D3(FOXD3)是FOX家族的重要成员,可以保持细胞簇的多能特性，神经嵴,和体内滋养祖细胞。已经证明FOXD3可以影响增殖，迁移,各种肿瘤的血管生成及其在生物体内的缺失和过度表达无疑将对细胞命运的改变和肿瘤的发生产生重要影响。然而,FOXD3在食管鳞状细胞癌(ESCC)中的潜在作用和分子机制尚未完全阐明.根据目前的研究,研究了FOXD3的表达水平和功能作用，阐明了其在ESCC肿瘤发生和发展中的预后价值和分子机制。FOXD3的表达水平在ESCC组织和细胞系中显著下调，与性别相关，上消化道肿瘤家族史,TNM阶段,入侵深度,淋巴结转移,和ESCC患者的生存。此外，FOXD3抑制细胞迁移和侵袭,参与TGF-β1诱导的上皮-间质转化过程。此外，在ESCC中,FOXD3与SMAD家族成员7(SMAD7)呈正相关.FOXD3可直接与SMAD7基因启动子区结合,导致SMAD7在人食管癌细胞中的转录促进。一起来看,FOXD3可能在ESCC中起肿瘤抑制作用，并可能作为ESCC的新治疗靶点和预后标志物。
